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Opioid Peptides of The Gut

Richard J. Miller, Lane D. Hirning

10.1002/cphy.cp060226

Source: Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology

Originally published: 1989

Published online: January 2011

Full Article on Wiley Online Library



Abstract

The sections in this article are:

1 Opioid Peptides
1.1 Pro‐opiomelanocortin
1.2 Proenkephalin A
1.3 Proenkephalin B
1.4 Morphine
2 Opioid Receptors
3 Opioid Peptide Processing Enzymes
4 Localization of Opioid Peptides and Receptors in Gut
4.1 Proenkephalin A
4.2 Proenkephalin B
4.3 Pro‐opiomelanocortin
5 Mechanism of Opioid Action in Gut
6 Physiological Functions of Endogenous Opioid Peptides
6.1 Gastrointestinal Motility
6.2 Antisecretory Actions of Opioid Peptides
6.3 Gallbladder and Bile Ducts
6.4 Opioid Effects on Pancreas
Figure 1. Figure 1.

Effect of purified pig brain extract on electrically induced contractions of isolated guinea pig myenteric plexus. Upper trace, inhibitory actions of extract (X, 100 μl) and normorphine (N, 50μg and 100 μg) as well as reduction of inhibitory activity by naloxone (NAL, 60 nM). Lower trace, inhibitory actions of extract and normorphine have recovered after washing tissue for 15 min. Reintroduction of naloxone into bath again reversed inhibition caused by extract.

From Hughes 132
Figure 2. Figure 2.

Diagram of three precursor peptides for endogenous opioid peptides.

From Höllt 126
Figure 3. Figure 3.

Processing of preproenkephalin A and preproenkephalin B.

From Lynch and Snyder 177). Reproduced with permission, from the Annual Review of Biochemistry, vol. 55. Copyright 1986 by Annual Reviews, Inc
Figure 4. Figure 4.

Enkephalin‐like immunoreactivity in nerves in whole mounts from normal small intestine of guinea pig. A: low‐power view of myenteric plexus. Immunoreactive nerve cells (arrows) apparent in myenteric ganglia (g). Double‐ended arrow indicates direction of circular muscle. Calibration: 200 μm. B: varicose immunoreactive fibers in ganglion of myenteric plexus. Calibration: 100 μm. C: nerve strands of myenteric plexus. Enkephalin‐like immunoreactivity is found in nerve fibers of primary (internodal) strands (1) of secondary strands running parallel to circular muscle (2), and of tertiary plexus (3). Branches running from secondary strands to circular muscle are broken off when circular layer removed (arrow). Calibration: 200 μm. D: detail of enkephalin fibers of tertiary plexus. Calibration: 100 μm. E, F: same area of circular muscle taken at two levels of focus, showing in E deep muscular plexus and in F nerve fibers in circular muscle. Fibers run parallel to direction of circular muscle. Calibration: 100 μm. G: varicose fibers with dotlike appearance in small bundles of deep muscular plexus, shown at higher magnification than in E. Calibration: 25 μm. H, I, J: nerve cell bodies with enkephalin‐like immunoreactivity in myenteric plexus. Cells have many short processes and one long process that sometimes has small spines emerging from it. Although not fluorescent, nuclei of these cell bodies are often not seen because of fluorescence of overlying cytoplasm. Calibration: 25 μm. K: submucosal gland of Brunner with loop network of reactive fibers. Acini of gland are seen as dark areas arranged as a rosette. Calibration: 50 μm. L: Reactive varicose fibers in submucous ganglion. No positive nerve cell bodies are present in these ganglia. Calibration: 50 μm. M: rare fibers of nonganglionated component of submucous plexus. Calibration: 50 μm.
Figure 5. Figure 5.

Cross sections of corpus of stomach (A), distal ileum (B), and proximal colon (C), demonstrating distribution and density of immunoreactive cell bodies () and nerve terminals () in various layers of gastrointestinal wall. Each panel is divided in two parts, one for rat (left) and one for guinea pig (right); results obtained with Met5‐enkephalin antiserum (, single fibers; , small numbers; , moderate numbers; , large numbers). Ratings of cells and nerve fibers follow. Cell bodies: ○ ○○, 1%–25%; , 26%–50%; , 51%–75%; , 76%–100%. Fibers: 1+, single fibers; 2 +, small numbers; 3+, moderate numbers; 4+, large numbers. All nerve fibers (except those around blood vessels) are drawn with two varicosities () or with one varicosity () (transversely cut fibers in longitudinal muscle layer). Number and distribution of fibers within a layer have been chosen to give visual impression of patterns observed in microscope.

From Schultzberg et al. 260). Copyright 1980. Reprinted with permission from Pergamon Press, Ltd
Figure 6. Figure 6.

Morphology of typical enteric enkephalin neuron. Cell bodies in ganglia of myenteric plexus send processes anally and circularly to supply circular muscle and deep muscular plexus beneath and up to ˜2 mm anal. Processes run orally to provide terminals in myenteric ganglia 3–4.5 mm away. Terminals in submucous ganglia (not shown) may arise as collaterals of processes running in deep muscular plexus. Cell bodies also provide terminals to tertiary plexus, close to and just oral to cells. Initial parts of orally directed processes are indicated by dashed lines because they were not directly observed. MP, myenteric plexus; CM, circular muscle; SM, submucosa. Longitudinal muscle not included.

From Furness et al. 90). Copyright 1983. Reprinted with permission from Pergamon Press, Ltd
Figure 7. Figure 7.

μ‐Receptors and κ‐receptors on single mouse dorsal root ganglion cell. Records are action potentials prolonged by presence of tetraethylammonium. When neuron was penetrated with an electrode containing potassium acetate (top), dynorphin (DYN, 1 μM), Leu‐enkephalin (L‐ENK, 10 μM), and morphiceptin (MC, 10 μM) all shortened the action potential. Potassium acetate electrode was withdrawn and same neuron reimpaled with cesium acetate electrode. Effect of dynorphin persisted, but actions of Leu‐enkephalin and morphiceptin were blocked. This suggests that dynorphin reduces spike duration by direct action on Ca2+ conductance, whereas morphiceptin and Leu‐enkephalin increase K+ conductance. This neuron probably has both μ‐ and κ‐receptors, because morphiceptin and dynorphin are quite selective; no conclusions can be drawn about existence of receptors. Concentrations of drugs are higher than those at neuron surface because they were applied by leakage from glass pipettes brought up to region of impaled cell.

From Werz and Macdonald 318


Figure 1.

Effect of purified pig brain extract on electrically induced contractions of isolated guinea pig myenteric plexus. Upper trace, inhibitory actions of extract (X, 100 μl) and normorphine (N, 50μg and 100 μg) as well as reduction of inhibitory activity by naloxone (NAL, 60 nM). Lower trace, inhibitory actions of extract and normorphine have recovered after washing tissue for 15 min. Reintroduction of naloxone into bath again reversed inhibition caused by extract.

From Hughes 132


Figure 2.

Diagram of three precursor peptides for endogenous opioid peptides.

From Höllt 126


Figure 3.

Processing of preproenkephalin A and preproenkephalin B.

From Lynch and Snyder 177). Reproduced with permission, from the Annual Review of Biochemistry, vol. 55. Copyright 1986 by Annual Reviews, Inc


Figure 4.

Enkephalin‐like immunoreactivity in nerves in whole mounts from normal small intestine of guinea pig. A: low‐power view of myenteric plexus. Immunoreactive nerve cells (arrows) apparent in myenteric ganglia (g). Double‐ended arrow indicates direction of circular muscle. Calibration: 200 μm. B: varicose immunoreactive fibers in ganglion of myenteric plexus. Calibration: 100 μm. C: nerve strands of myenteric plexus. Enkephalin‐like immunoreactivity is found in nerve fibers of primary (internodal) strands (1) of secondary strands running parallel to circular muscle (2), and of tertiary plexus (3). Branches running from secondary strands to circular muscle are broken off when circular layer removed (arrow). Calibration: 200 μm. D: detail of enkephalin fibers of tertiary plexus. Calibration: 100 μm. E, F: same area of circular muscle taken at two levels of focus, showing in E deep muscular plexus and in F nerve fibers in circular muscle. Fibers run parallel to direction of circular muscle. Calibration: 100 μm. G: varicose fibers with dotlike appearance in small bundles of deep muscular plexus, shown at higher magnification than in E. Calibration: 25 μm. H, I, J: nerve cell bodies with enkephalin‐like immunoreactivity in myenteric plexus. Cells have many short processes and one long process that sometimes has small spines emerging from it. Although not fluorescent, nuclei of these cell bodies are often not seen because of fluorescence of overlying cytoplasm. Calibration: 25 μm. K: submucosal gland of Brunner with loop network of reactive fibers. Acini of gland are seen as dark areas arranged as a rosette. Calibration: 50 μm. L: Reactive varicose fibers in submucous ganglion. No positive nerve cell bodies are present in these ganglia. Calibration: 50 μm. M: rare fibers of nonganglionated component of submucous plexus. Calibration: 50 μm.



Figure 5.

Cross sections of corpus of stomach (A), distal ileum (B), and proximal colon (C), demonstrating distribution and density of immunoreactive cell bodies () and nerve terminals () in various layers of gastrointestinal wall. Each panel is divided in two parts, one for rat (left) and one for guinea pig (right); results obtained with Met5‐enkephalin antiserum (, single fibers; , small numbers; , moderate numbers; , large numbers). Ratings of cells and nerve fibers follow. Cell bodies: ○ ○○, 1%–25%; , 26%–50%; , 51%–75%; , 76%–100%. Fibers: 1+, single fibers; 2 +, small numbers; 3+, moderate numbers; 4+, large numbers. All nerve fibers (except those around blood vessels) are drawn with two varicosities () or with one varicosity () (transversely cut fibers in longitudinal muscle layer). Number and distribution of fibers within a layer have been chosen to give visual impression of patterns observed in microscope.

From Schultzberg et al. 260). Copyright 1980. Reprinted with permission from Pergamon Press, Ltd


Figure 6.

Morphology of typical enteric enkephalin neuron. Cell bodies in ganglia of myenteric plexus send processes anally and circularly to supply circular muscle and deep muscular plexus beneath and up to ˜2 mm anal. Processes run orally to provide terminals in myenteric ganglia 3–4.5 mm away. Terminals in submucous ganglia (not shown) may arise as collaterals of processes running in deep muscular plexus. Cell bodies also provide terminals to tertiary plexus, close to and just oral to cells. Initial parts of orally directed processes are indicated by dashed lines because they were not directly observed. MP, myenteric plexus; CM, circular muscle; SM, submucosa. Longitudinal muscle not included.

From Furness et al. 90). Copyright 1983. Reprinted with permission from Pergamon Press, Ltd


Figure 7.

μ‐Receptors and κ‐receptors on single mouse dorsal root ganglion cell. Records are action potentials prolonged by presence of tetraethylammonium. When neuron was penetrated with an electrode containing potassium acetate (top), dynorphin (DYN, 1 μM), Leu‐enkephalin (L‐ENK, 10 μM), and morphiceptin (MC, 10 μM) all shortened the action potential. Potassium acetate electrode was withdrawn and same neuron reimpaled with cesium acetate electrode. Effect of dynorphin persisted, but actions of Leu‐enkephalin and morphiceptin were blocked. This suggests that dynorphin reduces spike duration by direct action on Ca2+ conductance, whereas morphiceptin and Leu‐enkephalin increase K+ conductance. This neuron probably has both μ‐ and κ‐receptors, because morphiceptin and dynorphin are quite selective; no conclusions can be drawn about existence of receptors. Concentrations of drugs are higher than those at neuron surface because they were applied by leakage from glass pipettes brought up to region of impaled cell.

From Werz and Macdonald 318
References
 1. Adler, H. F., A. I., Atkinson, and A. C. Ivy, Effect of morphine and dilaudid on the ileum and of morphine, dilaudid and atropine on the colon of man. Arch. Intern. Med. 69: 974–985, 1942.
 2. Aggestrup, S., and S. J. Jensen, Effects of regulatory peptides on the porcine lower oesophageal sphincter. Regul. Pept. 4: 155–162, 1982.
 3. Akil, H., E., Young, S. J. Watson, and D. H. Coy, Opiate binding properties of naturally occurring N‐ and C‐terminus modified β‐endorphins. Peptides Fayetteville 2: 289–292, 1981.
 4. Alumets, J., J., Fahrenkrug, R. Håkanson, O. Schafalitzky De Muckadell, F. Sundler, and R. Uddman, A rich VIP nerve supply is characteristic of sphincters. Nature Lond. 280: 155–156, 1979.
 5. Alumets, J., S., Falkmer, L. Crimelius, R. Håkanson, O. Ljungberg, F. Sundler, and E. Wilander, Immunocyto‐chemical demonstration of enkephalin and β‐endorphin in endocrine tumors of the rectum. Acta Pathol. Microbiol. Scand. Sect. B Microbiol. 88: 103, 1980.
 6. Alumets, J., R., Håkanson, F. Sundler, and K.‐J. Chang, Leu‐enkephalin‐like material in nerves and enterochromaffin cells in the gut. Histochem. J. 56: 187–196, 1978.
 7. Ambinder, R. J., and M. M. Schuster, Endorphins: new gut peptides with a familiar face. Gastroenterology 77: 1132–1140, 1979.
 8. Anderson, W., E., Molina, J. Reutz, and B. Hirshowitz, Analysis of the 2‐deoxy‐D‐glucose induced vagal stimulation of gastric secretion and gastrin release in dogs using methionine enkephlin, morphine, and naloxone. J. Pharmacol. Exp. Ther. 222: 617–621, 1982.
 9. Asaoka, H., and M. Oouchi, Effects of morphine on the guinea pig biliary tract. Eur. J. Pharmacol. 80: 311–316, 1982.
 10. Back, S. A., and C. Gorenstein, Localization of neutral metalloendopeptidase (enkephalinase) activity in rat brain by fluorescent histochemistry. Soc. Neurosci. Abstr. 15: 389, 1985.
 11. Bardon, T., and Y. Ruckebusch, Comparative effects of opiate agonist on proximal and distal colonic motility in dogs. Eur. J. Pharmacol. 110: 329–334, 1985.
 12. Barnea, A., G., Cho, and J. C. Porter, Apparent cosequestration of immunoreactive corticotropin, α‐melanotropin, and β‐lipotropin in hypothalamic granules. J. Neurochem. 36: 1083–1092, 1981.
 13. Bartho, L., P., Holzer, J. Donnerer, and F. Lembeck, Evidence for the involvement of substance P in the atropine‐resistant peristalsis of the guinea pig ileum. Neurosci. Lett. 32: 69–74, 1982.
 14. Bass, P., and J. N. Wiley, Effects of ligation and morphine on electric and motor activity of dog duodenum. Am. J. Physiol. 208: 908–913, 1965.
 15. Behar, J., and P. Biancani, Effect of cholecystokinin and the octapeptide of cholecystokinin on the feline sphincter of Oddi and gallbladder. J. Clin. Invest. 66: 1231–1239, 1980.
 16. Behar, J., and P. Biancani, Effect of naloxone on the cat sphincter of Oddi (SO): evidence for a physiologic role of opioid peptides in the regulation of the sphincter of Oddi. In: Gastrointestinal Motility, edited by M. Weinbeck. New York: Raven, 1982, p. 397–403.
 17. Bianchi, G., P., Ferretti, M. Recchia, M. Rocchetti, A. Tavani, and L. Manara, Morphine tissue levels and reduction of gastrointestinal transit in rats. Gastroenterology 85: 852–858, 1983.
 18. Bickel, M., Stimulation of colonic motility in dogs and rats by an enkephalin analogue pentapeptide. Life Sci. 33, Suppl. 1: 469–472, 1983.
 19. Binder, H. J., J. P., Laurenson, and J. W. Dobbins, Role of opiate receptors in regulation of enkephalin stimulation of active sodium and chloride absorption. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10) 247: G432–G436, 1984.
 20. Bitar, K. N., and G. M. Makhlouf, Selective presence of opiate receptors on intestinal circular muscle cells. Life Sci. 37: 1545–1550, 1985.
 21. Boarder, M. R., A. J., Lockfeld, and J. D. Barchas, Met‐enkephalin Arg6, Phe7 immunoreactivity in bovine caudate and bovine adrenal medulla. J. Neurochem. 39: 149–154, 1982.
 22. Bornstein, J. C., M., Costa, J. B. Fukness, and G. M. Lees, Electrophysiology and enkephalin immunoreactivity of identified myenteric plexus neurones of guinea‐pig small intestine. J. Physiol. Lond. 351: 313–325, 1984.
 23. Bradbury, A. F., M. D. A., Finnie, and D. G. Smyth, Mechanism of C‐terminal amide formation by pituitary enzymes. Nature Lond. 298: 686–688, 1982.
 24. Brown, D. R., and R. J. Miller, CNS involvement in the antisecretory action of [Met5]‐enkephalinamide on the rat intestine. Eur. J. Pharmacol. 90: 441–444, 1983.
 25. Bruni, J. F., W. B., Watkins, and S. C. Yens, β‐endorphin in the human pancreas. J. Clin. Endocrinol. Metab. 49: 649–651, 1979.
 26. Bueno, L., and J. Fioramonti, A possible central serotonergic mechanism involved in the effects of morphine on colonic motility in the dog. Eur. J. Pharmacol. 83: 147–153, 1982.
 27. Bueno, L., F., Fioramonti, V. Rayner, and Y. Ruckebush, Effects of motilin, somatostatin and pancreatic polypeptide on the migrating myoelectric complex in pig and dog. Gastroenterology 82: 1395–1402, 1982.
 28. Bueno, L., J., Fioramonti, C. Honde, M. J. Faregeas, and M. P. Primi, Central and peripheral control of gastrointestinal and colonic motility by endogenous opiates in conscious dogs. Gastroenterology 88: 549–557, 1985.
 29. Bu'Lock, A. J., C., Vaillant, G. J. Dockray, and J. D. Bu'Lock, A rational approach to the fixation of peptidergic nerve cell bodies in the gut using parabenzoquinone. Histochemistry 74: 49–55, 1982.
 30. Bunnett, N. W., R., Kobayashi, M. S. Orloff, J. R. Reeve, JR., A. J. Turner, and J. H. Walsh, Catabolism of gastrin releasing peptide and substance P by gastric membrane bound peptidases. Peptides Fayetteville 6: 277–283, 1985.
 31. Burks, T. F., Mediation by 5‐hydroxytryptamine of morphine stimulant actions in dog intestine. J. Pharmacol. Exp. Ther. 185: 530–539, 1973.
 32. Burks, T. F., Acute effects of morphine on rat intestinal motility. Eur. J. Pharmacol. 40: 279–283, 1976.
 33. Burks, T. F., Actions of drugs on gastrointestinal motility. In: Physiology of the Gastrointestinal Tract (1st ed.), edited by L. R. Johnson. New York: Raven, 1981, p. 495–534.
 34. Burks, T. F., J. J., Gallican, and F. Porreca, Gastrointestinal drug receptors. J. Clin. Gastroenterol. 5: 29–36, 1983.
 35. Burks, T. F., L. D., Hirning, J. J. Galligan, and T. P. Davis, Motility effects of opioid peptides in dog intestine. Life Sci. 31: 2237–2240, 1982.
 36. Burks, T. F., and J. P. Long, Release of intestinal 5‐hydroxytryptamine by morphine and related agents. J. Pharmacol. Exp. Ther. 267–276, 1976.
 37. Burks, T. F., and J. P. Long, Responses of isolated dog small intestine to analgesic agents. J. Pharmacol. Exp. Ther. 158: 264–271, 1976.
 38. Burleigh, D. E., J. J., Galligan, and T. F. Burks, Subcutaneous morphine reduces intestinal propulsion in rats partly by a central action. Eur. J. Pharmacol. 75: 283–287, 1981.
 39. Canfield, S. P., and J. Spencer, The action of morphine and naloxone on acid secretion by the rat isolated stomach. Eur. J. Pharmacol. 71: 135–138, 1981.
 40. Carter, R. J., S., Shuster, and J. S. Morley, Melanotropin potentiating factor is the C‐terminal tetrapeptide of human β‐lipotropin. Nature Lond. 279: 74–75, 1979.
 41. Cetin, Y., D., Aunis and D. Grube, Gastrointestinal enterochromaffin cells: co‐localization of serotonin, prodynorphin derived peptides and chromogram A (Abstract). Regul. Pept. 13: 94, 1985.
 42. Chaillet, P., H., Marçais‐Collado, J. Costentin, C. Yi, S. De La Baume, and J. C. Schwartz, Inhibition of enkephalin metabolism by, and an antinociceptive activity of, bestatin an aminopeptidase inhibitor. Eur. J. Pharmacol. 86: 329–336, 1983.
 43. Champion, M. L., S. N., Sullivan, S. R. Bloom, T. E. Adrian, and N. D. Christofides, The effects of naloxone and morphine on postpandial gastrointestinal hormone secretion. Am. J. Gastroenterol. 77: 617–620, 1982.
 44. Chang, K.‐J., A., Killian, E. Hazum, P. Cuatrecasas, and J. ‐K. Chang, Morphiceptin (NH4‐Tyr‐Pro‐Phe‐Pro‐CoNH2): a potent and specific agonist for morphine (μ) receptors. Science Wash. DC 212: 75–77, 1981.
 45. Chavkin, C., and A. Goldstein, Demonstration of a specific dynorphin receptor in guinea pig ileum myenteric plexus. Nature Lond. 291: 591–593, 1981.
 46. Cherubini, E., and R. A. North, μ And κ opioids inhibit transmitter release by different mechanisms. Proc. Natl. Acad. Sci. USA 82: 1860–1863, 1985.
 47. Chrétien, M., and N. G. Seidah, Chemistry and biosynthesis of pro‐opiomelanocortin, ACTH, MSH's, endorphins and their related peptides. Mol. Cell. Biochem. 34: 101–127, 1981.
 48. Clark, S. J., and T. W. Smith, Peristalsis abolishes the release of methionine‐enkephalin from guinea‐pig ileum in vitro. Eur. J. Pharmacol. 70: 421–424, 1981.
 49. Corbett, A. D., M. G. C., Gillan, H. W. Kosterlitz, A. T. Mcknight, S. J. Paterson, and L. E. Robson, Selectivities of opioid peptide analogues as agonists and antagonists at the δ‐receptor. Br. J. Pharmacol. 83: 271–279, 1984.
 50. Costa, M., J. B., Furness, and A. C. Cuello, Separate populations of opioid containing neurons in the guinea‐pig intestine. Neuropeptides 5: 445–448, 1985.
 51. Cotton, R., H. W., Kosterlitz, S. J. Paterson, M. J. Rance, and J. R. Traynor, The use of [3H]‐[D‐Pen2,D‐Pen5] enkephalin as a highly selective ligand for the δ‐binding site. Br. J. Pharmacol. 84: 927–932, 1985.
 52. Cowan, A., and D. Gmerek, In vivo studies with ICI 154129, a putative δ‐receptor antagonist. Life Sci. 31: 2213–2216, 1982.
 53. Crochelt, R. F., E., Shaw, and S. R. Peikin, Enkephalins mediate cholecystokinin‐induced gallbladder contraction in the guinea‐pig. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 179.
 54. Dahl, J. C., M. L., Epstein, B. C. Silva, and I. Lindberg, Multiple immunoreactive forms of Met and Leu‐enkephalin in fetal and neonatal rat brain and in rat gut. Life Sci. 31: 1853–1856, 1982.
 55. Daniel, E. E., Pharmacology of adrenergic, cholinergic and drugs acting on other receptors in gastrointestinal muscle. In: Mediators and Drugs in Gastrointestinal Motility, edited by G. Bertaccini. New York: Springer‐Verlag, 1982, p. 249–322.
 56. Daniel, E. E., M., Costa, J. B. Furness, and J. R. G. Keast, Peptide neurons in the canine small intestine. J. Comp. Neurol. 237: 227–238, 1985.
 57. Danquechin Dorval, E., G. P. Mueller, R. Eng, A. Durarovic, J. Conklin, and A. Dubois, Involvement of endogenous opiates in radiation‐induced suppression of gastric emptying. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 157–158.
 58. De La Baume, S., C. C. Yi, J. C. Schwartz, P. Chaillet, H. Marcais‐Collado, and J. Costentin, Participation of both ‘enkephalinase’ and aminopeptidase activities in the metabolism of endogenous enkephalins. Neuroscience 8: 143–151, 1983.
 59. Dobbins, J., L., Racusen, and H. J. Binder, Effect of D‐alanine methionine enkephalin amide on ion transport in rabbit ileum. J. Clin. Invest. 66: 19–28, 1980.
 60. Docherty, K., and D. F. Steiner, Post‐translational proteolysis in polypeptide hormone biosynthesis. Annu. Rev. Physiol. 44: 625–638, 1982.
 61. Donnerer, J., P., Holzer, and F. Lembeck, Release of dynorphin, somatostatin and substance P from the vascularly perfused small intestine of the guinea‐pig during peristalsis. Br. J. Pharmacol. 83: 919–925, 1984.
 62. Douglas, S. J., O., Civelli, and E. Herbert, Poly protein gene expression: generation of diversity of neuroendocrine peptides. Annu. Rev. Biochem. 53: 665–715, 1984.
 63. Drouin, J., and H. M. Goodman, Most of the coding region of rat ACTH β‐LPH precursor gene lacks intervening sequences. Nature Lond. 288: 610–612, 1980.
 64. Duggan, A. W., and R. A. North, Electrophysiology of opioids. Pharmacol. Rev. 35: 219–281, 1984.
 65. Dushwood, M. R., E. S., Debnam, J. Bagnall, and C. S. Thompson, Autoradiographic localization of opiate receptors in rat small intestine. Eur. J. Pharmacol. 107: 267–269, 1985.
 66. Edin, R., J., Lundberg, L. Terenius, A. Dahlström, T. Hökfelt, J. Kewenter, and H. Ahlman, Evidence for vagal enkephalinergic neural control of the pylorus and stomach. Gastroenterology 78: 492–497, 1980.
 67. Eipper, B. A., and R. E. Mains, Analysis of the common precursor to corticotropin and endorphin. J. Biol. Chem. 253: 5732–5744, 1978.
 68. Eipper, B. A., and R. E. Mains, Structure and biosynthesis of pro‐adrenocorticotropin/endorphin and related peptides. Endocr. Rev. 1: 1–27, 1980.
 69. Ekblad, E., M., Ekelund, H. Graffner, R. Håkanson, and F. Sundler, Peptide‐containing nerve fibers in the stomach wall of rat and mouse. Gastroenterology 89: 73–85, 1985.
 70. Elde, R., T., Hökfelt, O. Johansson, and L. Terenius, Immunohistochemical studies using antibodies to leucine enkephalin: initial observations on the nervous system of the rat. Neurosci. Lett. 1: 349–351, 1976.
 71. Erdös, E. G., A. L., Johnson, and N. T. Boyden, Hydrolysis of enkephalin by cultured human endothelial cells and by purified peptidyl dipeptidase. Biochem. Pharmacol. 27: 843–848, 1978.
 72. Erdös, E. G., and R. A. Skidgel, Structure and functions of human angiotensin I converting enzyme (kininase II). Biochem. Soc. Trans. 13: 35–54, 1985.
 73. Feldman, M., J. H., Walsh, and I. L. Taylor, Effect of naloxone and morphine on gastric acid secretion and on serum gastrin and pancreatic polypeptide concentrations in humans. Gastroenterology 79: 294–298, 1980.
 74. Ferri, G. L., R. A., Morreale, L. Soimero, and G. J. Dockray, Differential distribution of Met‐enkephalin‐Arg6‐Gly7‐Leu8 (MERGL) immunoreactivity in the ileocecal and sigmoid‐rectal‐anal regions of the human gut (Abstract). Regul. Pept. 13: 99, 1985.
 75. Ferri, G. L., R. A., Morreale, L. Soimero, and G. J. Dockray, Intramural distribution and characterization of Met‐enkephalin‐Arg6‐Gly7‐Leu8 (MERGL) immunoreactivity in the human gut (Abstract). Regul. Pept. 13: 99, 1985.
 76. Feurle, G. E., V., Helmstaedter, and U. Weber, Met‐ and Leu‐enkephalin immuno‐ and bio‐reactivity in human stomach and pancreas. Life Sci. 31: 2961–2969, 1982.
 77. Feurle, G. E., U., Weber, and V. Helmstaedter, β‐Lipotropin‐like material in human pancreas and pyloric antral mucosa. Life Sci. 27: 467–473, 1980.
 78. Fioramonti, J., L., Buéno, and M. J. Fargaes, Enhancement of colonic motor response to feeding by central endogenous opiates in dogs. Life Sci. 36: 2509–2514, 1985.
 79. Fioramonti, J., M. J., Fargeas, and L. Buéno, Different targets for i.v. vs. i.c.v. administered morphine for its effect on colonic motility in dogs. Eur. J. Pharmacol. 117: 115–120, 1985.
 80. Fontaine, J., and J. Reuse, Contractor responses of the isolated colon of the mouse to morphine and some opioid peptides. Br. J. Pharmacol. 85: 861–867, 1985.
 81. Forssmann, W. G., U., Helmstaedter, and G. Feurle, Relationship of enkephalin and endorphin immunoreactivity with D‐cells and G‐cells of the stomach (Abstract). Acta Hepato‐Gastroenterol. 24: 488, 1977.
 82. Fox, J. E. T., and J. Kraicer, Immunoreactive α‐melanocyte stimulating hormone, its distribution in the gastrointestinal tract of intact hypophysectomized rats. Life Sci. 28: 2127–2132, 1981.
 83. Fox, J. E. T., N. S., Track, and E. E. Daniel, Relationship of plasm motilin concentration to fat ingestion, duodenal acidification and alkalinization and migrating motor complexes in dogs. Can. J. Physiol. Pharmacol 59: 180–186, 1981.
 84. Fricker, L. D., T. H., Plummer, and S. H. Snyder, Enkephalin convertase potent, selective, and irreversible inhibitors. Biochem. Biophys. Res. Commun. 111: 994–1000, 1983.
 85. Fricker, L. D. AND S. H. Snyder, Enkephalin convertase: purification and characterization of a specific enkephalin‐synthesizing carboxypeptidase localized to adrenal chromaffin granules. Proc. Natl. Acad. Sci. USA 79: 3886–3890, 1982.
 86. Fricker, L. D., and S. H. Snyder, Purification and characterization of enkephalin convertase, an enkephalin‐synthesizing carboxypeptidase. J. Biol. Chem. 258: 10950–10955, 1983.
 87. Fritsch, H. A. R., S. Van, Noorden and A. G. E. Pearse, Gastrointestinal and neurohumoral peptides in the alimentary tract and cerebral complex of Ciona intestinalis (Ascidiaceae). Cell Tissue Res. 223: 369–402, 1982.
 88. Furness, J. B., and M. Costa, Types of nerves in the enteric nervous system. Neuroscience 5: 1–20, 1979.
 89. Furness, J. B., M., Costa, I. L. Gibbins, I. J. Llewellyn‐Smith, and J. R. Oliver, Neurochemically similar myenteric and submucous neurones directly traced to the mucosa of the small intestine. Cell Tissue Res. 241: 155–163, 1985.
 90. Furness, J. B., M., Costa, and R. J. Miller, Distribution and projections of nerves with enkephalin‐like immunoreactivity in the guinea‐pig small intestine. Neuroscience 8: 653–604, 1983.
 91. Furness, J. B., M., Costa, R. Murphy, A. M. Beardsley, J. R. Oliver, I. J. Llewellyn‐Smith, R. L. Eskay, A. B. Shulkes, T. W. Moody, and D. M. Meyer, Detection and characterization of neurotransmitters, particularly peptides in the gastrointestinal tract. Scand. J. Gastroenterol. 17: 61–70, 1982.
 92. Gacel, G., M. C., Fournie‐Zaluski, and B. P. Rogues, D‐Tyr‐Ser‐Gly‐Phe‐Leu‐Thr, a highly preferential ligand to δ‐opiate receptors. FEBS Lett. 118: 245–247, 1980.
 93. Gaginella, T., and Z. C. Wu, [D‐Ala2, D‐Met5NH2]‐enkephalin inhibits acetylcholine release from the submucous plexus of rat colon. J. Pharm. Pharmacol. 35: 823–825, 1983.
 94. Galligan, J. J., and T. F. Burks, Inhibition of gastric and intestinal motility by centrally and periphrally administered morphine. Proc. West. Pharmacol. Soc. 25: 307–311, 1982.
 95. Galligan, J. J., and T. F. Burks, Opioid peptides inhibit intestinal transit in the rat by a central mechanism. Eur. J. Pharmacol. 85: 61–68, 1982.
 96. Galligan, J. J., and T. F. Burks, Centrally mediated inhibition of small intestinal transit and motility by morphine in the rat. J. Pharmacol. Exp. Ther. 226: 356–361, 1983.
 97. Galligan, J. J., H. I., Mosberg, R. Huret, V. J. Hruby, and T. F. Burks, Cerebral δ‐opioid receptors mediate analgesia but not the intestinal motility effects of intracerebroventricularly administered opioids. J. Pharmacol. Exp. Ther. 229: 641–648, 1984.
 98. Gee, C. E., C.‐L. C., Chen, J. L. Roberts, R. Thompson, and S. J. Watson, Identification of pro‐opiomelanocortin neurones in rat hypothalamus by in situ cDNA‐mRNA hybridization. Nature Lond. 306: 374–376, 1983.
 99. Gee, N. S., R., Matsas, and J. A. Kenny, A monocolonal antibody to kidney endopeptidase‐24.11. Biochem. J. 214: 377–386, 1983.
 100. Gillian, M. G. C., and D. Pollock, Acute effects of morphine and opioid peptides on the motility and responses of rat colon to electrical stimulation. Br. J. Pharmacol. 68: 381–392, 1980.
 101. Gintzler, A. R., and J. A. Scalisi, Effects of opioids on non‐cholinergic excitatory responses of the guinea pig isolated ileum: inhibition of release of enteric substance P. Br. J. Pharmacol. 75: 199–205, 1982.
 102. Giraud, A. S., G. J., Dockray, and R. G. Williams, Immunoreactive Met‐enkephalin‐Arg6 in rat brain and bovine brain, gut and adrenal. J. Neurochem. 43: 1236–1242, 1984.
 103. Giraud, A. S., R. C., Williams, and G. J. Dockray, Evidence for different patterns of post‐translational processing of pro‐enkephalin in the bovine adrenal, colon and striatum indicated by radioimmunoassay using region‐specific antisera to Met‐Enk‐Arg6‐Phe7 and Met‐Enk‐Arg6‐Gly7‐Leu8. Neurosci. Lett. 46: 223–228, 1984.
 104. Gmerek, D. E., A., Cowan, and J. H. Woods, Distinct peripheral and central sites for morphine‐induced inhibitor of gastrointestinal transit in rats. Pharmacologist 25: 208, 1983.
 105. Gmerek, D. E., A., Cowan, and J. H. Woods, Independent central and peripheral mediation of morphine induced inhibition of gastrointestinal transit in rats. J. Pharmacol. Exp. Ther. 236: 8–14, 1986.
 106. Goldstein, A., R. W., Barrett, I. F. James, L. I. Lowney, C. J. Weitz, L. L. Knipmeyer, and H. Rapoport, Morphine and other opiates from beef brain and adrenal. Proc. Natl. Acad. Sci. USA 82: 5203–5207, 1985.
 107. Goldstein, A., L. I., Lowney, and B. K. Pal, Stereospecific and nonspecific interaction of the morphine congene levorphanol in subcellular fractions of mouse brain. Proc. Natl. Acad. Sci. USA 68: 1742–1747, 1971.
 108. Gorenstein, C., and S. H. Snyder, Enkephalinases. Proc. R. Soc. Lond. B. Biol. Sci. 210: 123–132, 1980.
 109. Goyal, R. K., and B. W. Cobb, Motility of the pharynx esophagus and the esophigeal sphincters. In: The Physiology of the Gastrointestinal Tract (1st ed.), edited by L. R. Johnson. New York: Raven, 1981, p. 359–392.
 110. Gramsch, C., G., Kleber, V. Höllt, A. Pasi, P. Mehraein, and A. Herz, Pro‐opiocortin fragments in human and rat brain: β‐endorphin and α‐MSH are the predominant peptides. Brain Res. 192: 109–119, 1980.
 111. Grevel, J. and W. Sadee, An opiate binding site in the rat brain is highly selective for 4,5‐epoxymorphinans. Science Wash. DC 221: 1198–1201, 1983.
 112. Gros, C., S. B., Giro, and J. C. Schwartz, Identification of aminopeptidease M as an enkephalin‐inactivating enzyme in rat cerebral membranes. Biochemistry 24: 2179–2185, 1985.
 113. Gros, C., S. B., Giro, and J. C. Schwartz, Purification of membrane bound aminopeptidase from rat brain: identification of aminopeptidase M. Neuropeptides 5: 485–488, 1985.
 114. Grossman, M. I., Regulation of gastric acid secretion. In: Physiology of the Gastrointestinal Tract (1st ed.), edited by L. R. Johnson. New York: Raven, 1981, p. 659–672.
 115. Grube, D., Immunoreactivities of gastrin (G‐) cells. II. Nonspecific binding of immunoglobins to G‐cells by ionic interactions. Histochemistry 66: 149–167, 1980.
 116. Grube, D., β‐endorphin‐like immunoreactivity in plasma cells of the canine colonic mucosa. Histochemistry 69: 157–160, 1980.
 117. Grube, D., K. H., Voigt, and E. Weber, Pancreatic glucagon cells contain endorphin‐like immunoreactivity. Histochemistry 59: 75–79, 1978.
 118. Grube, D., and E. Weber, Immunoreactivities of gastrin (G‐) cells. I. Dilution‐dependent staining of G‐cells by antisera and non‐immune sera. Histochemistry 65: 223–237, 1980.
 119. Hall, A. W., A. R., Moosa, A. Clark, G. R. Cooley, and D. B. Skinner, The effect of premedication drugs on the lower esophageal high pressure zone and reflux status of Rhesus monkeys and man. Gut 16: 347–352, 1975.
 120. Han, J. S., H., Fei, and Z. F. Zhou, Met‐enkephalin‐Arg6‐Phe7‐like immunoreactive substances mediate electroacupuncture analgesia in the periaqueductal gray of the rabbit. Brain Res. 322: 289–296, 1984.
 121. Hautefeuille, M., V., Brantl, A‐M. Dumontier, and J‐F. Desjeux, In vitro effects of β‐casomorphins on ion transport in rabbit ileum. Am. J. Physiol. 250 (Gastrointest. Liver Physiol. 13): G92–G97, 1986.
 122. Hayes, A. G., and M. B. Tyers, Determination of receptors that mediate opiate side effects in the mouse. Br. J. Pharmacol. 79: 731–736, 1983.
 123. Hersh, L., Characterization of membrane‐bound aminopeptidases from rat brain: identification of the enkephalin‐degrading aminopeptidase. J. Neurochem. 44: 1427–1435, 1985.
 124. Hirning, L. D., V. J., Hruby, R. Hurst, and T. F. Burks, Differential effects of μ‐, κ‐, and δ‐agonists on motility of the canine small intestine ex vivo (Abstract). Soc. Neurosci. 10: 1115, 1984.
 125. Hirning, L. D., F., Porreca, and T. F. Burks, μ, But not κ, opioid agonists induce contractions of the canine small intestine ex vivo. Eur. J. Pharmacol. 109: 49–54, 1985.
 126. Höllt, V., Multiple endogenous opioid peptides, Trends Neurosci. 6: 24–32, 1983.
 127. Holmgren, S., J., Jensen, A.‐C. Jonsson, K. Lundin, and S. Nilsson, Neuropeptides in the gastrointestinal canal of Necturus maculosus. Cell Tissue Res. 241: 565–580, 1985.
 128. Holzer, P., and F. Lembeck, Neurally mediated contraction of ileal longitudinal muscle by substance P. Neurosci. Lett. 17: 101–105, 1980.
 129. Hook, V. Y. H., and Y. P. Loh, Carboxypeptidase B‐like converting enzyme activity in secretory granules of rat pituitary. Proc. Natl. Acad. Sci. USA 81: 2776–2780, 1984.
 130. Houck, J. C., C. M., Chang, and C. D. Kimball, Pancreatic β‐endorphin‐like polypeptides. Pharmacology 23: 14–23, 1981.
 131. Howard, J. M., M. R., Belsheim, and S. N. Sullivan, Enkephalin inhibits relaxation of the lower esophageal sphincter. Br. Med. J. 285: 1605–1606, 1982.
 132. Hughes, J., Isolation of an endogenous compound from the brain with pharmacological properties similar to morphine. Brain Res. 88: 295–306, 1975.
 133. Hughes, J., H. W., Kosterlitz, and T. W. Smith, The distribution of methionine‐enkephalin and leucine‐enkephalin in the brain and peripheral tissues. Br. J. Pharmacol. 61: 639–647, 1977.
 134. Hughes, J., T. W., Smith, H. W. Kosterlitz, L. H. Fothergill, B. A. Morgan, and H. Morris, Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature Lond. 255: 577–579, 1975.
 135. Huidobro‐Toro, J. P., and E. L. Way, Contractile effect of morphine and related opioid alkaloids, β‐endorphin and methionine enkephalin on the isolated colon from Long Evans rats. Br. J. Pharmacol. 74: 681–694, 1981.
 136. Ipp, E., J., Dharajiwala, W. Pugh, A. R. Moossa, and A. H. Rubenstein, Effects of an enkephalin analogue on pancreatic endocrine function and glucose homeostasis in normal endocrine function and glucose homeostasis in normal and diabetic dogs. Endocrinology 111: 2110–2116, 1982.
 137. Ipp, E., G., Garberoglio, H. Richter, A. R. Moosa, and A. H. Rubenstein, Naloxone decreases centrally induced hyperglycemia in dogs. Evidence for an opioid role in glucose homeostasis. Diabetes 33: 619–621, 1984.
 138. Ipp, E., V., Schusdziarra, V. Harris, and R. N. Unger, Morphine‐induced hyperglycemia: role of insulin and glucagon. Endocrinology 107: 461–463, 1980.
 139. Ito, S., K., Takai, A. Shibata, Y. Matsubara, and N. Yanaihara, Met‐enkephalin‐immunoreactive and gastrin reactive cells in the human and canine pyloric antrum. Gen. Comp. Endocrinol. 38: 238–245, 1979.
 140. Japfe, J. H. and W. R. Martin, Opioid analgesics and antagonists. In: The Pharmacological Basis of Therapeutics (7th ed.), edited by A. G. Gilman, L. S. Goodman, T. W. Rail, and F. Murad. New York: Macmillan 1985, p. 491–531.
 141. Jean, A., J. P., Miolan, and C. Roman, In vitro study of the effects of Leu‐enkephalin and related drugs on the vagally induced responses of the cat lower esophageal sphincter. In: Gastrointestinal Motility, edited by C. Roman. Lancaster, UK: MTP, 1984, p. 29–36.
 142. Jessen, K. R., M. J., Saffrey, S. Van Noorden, S. R. Bloom, J. M. Polak, and G. Burnstock, Immunohistochemical studies of the enteric nervous system in tissue culture and in situ: localization of vasoactive intestinal polypeptide (VIP), substance P and enkephalin immunoreactive nerves in the guinea‐pig gut. Neuroscience 5: 1717–1736, 1980.
 143. Jivegård, L., E., Thornell, S. Björck, and J. Svanvik, The effects of morphine and enkephalin on gallbladder function in experimental cholecystitis. Inhibition of inflammatory gallbladder secretion. Scand. J. Gastroenterol. 20: 1049–1056, 1985.
 144. Kachur, J. F., and R. J. Miller, Characterization of the opiate receptor in the guinea‐pig ileal mucosa. Eur. J. Pharmacol. 81: 177–183, 1982.
 145. Kachur, J. F., R. J., Miller, and M. Field, Control of guinea‐pig intestinal electrolyte secretion by a S‐opiate receptor. Proc. Natl. Acad. Sci. USA 77: 2753–2756, 1982.
 146. Kakidani, H., Y., Furutani, H. Takahashi, M. Noda, Y. Morimota, T. T. Hirose, M. Asai, S. Inayama, S. Nakanishi, and S. Numa, Cloning sequence analysis of cDNA for porcine α‐neoendorphin/dynorphin precursor. Nature Lond. 298: 245–249, 1982.
 147. Kamikawa, Y., and V. Shimo, Pharmacologic characterization of the opioid receptor in the submucous plexus of the guinea‐pig oesophagus. Br. J. Pharmacol. 78: 693–699, 1983.
 148. Katayama, Y., G. M., Lees, and G. T. Pearson, Electrophysiological and morphological similarities between guinea‐pig myenteric plexus neurones showing immunoreactivity to enkephalins (enk) vasoactive intestinal peptide (VIP) (Abstract). Br. Neuroendocrine Group 1985.
 149. Katayama, Y., G. M., Lees, and G. T. Pearson, Electrophysiological and morphological characteristics of vasoactive intestinal peptide (VLP)‐immunoreactive neurones in the guinea‐pig myenteric plexus. J. Physiol. Lond. 378: 1–11, 1986.
 150. Keast, J. R., J. B., Furness, and M. Costa, Origins of peptide and norepinephrine nerves in the mucosa of the guinea‐pig small intestine. Gastroenterology 86: 637–644, 1984.
 151. Keast, J. R., J. B., Furness, and M. Costa, Distribution of certain peptide‐containing nerve fibers and endocrine cells in the gastrointestinal mucosa in five mammalian species. J. Comp. Neurol. 236: 403–422, 1985.
 152. Khachaturian, H., M. E., Lewis, M. K. Schafer, and S. J. Watson, Anatomy of the CNS opioid system. Trends Neurosci. 8: 111–119, 1985.
 153. Konturek, S. J., N., Kwiecien, W. Obtulowicz, J. Swierczek, W. Bielanski, J. Oleksy, and D. H. Coy, Effect of enkephalin and naloxone on gastric acid and serum gastrin and pancreatic polypeptide concentration in humans. Gastroenterology 24: 740–745, 1983.
 154. Konturek, S. J., T., Tasler, M. Cieszkowski, E. Mikos, D. H. Coy, and A. V. Schally, Comparison of methionine enkephalin and morphine in the stimulation of gastric acid secretion in the dog. Gastroenterology 78: 294–300, 1980.
 155. Koslo, R. J., T. F., Burks, and F. Porreca, Centrally administered bombesin affects gastrointestinal transit and colonic bead expulsion through a supraspinal mechanism. J. Pharmacol. Exp. Ther. 238: 62–67, 1986.
 156. Kosterlitz, H. W., and A. A. Waterfield, In vitro models in the study of structure‐activity relationships of narcotic activity. Ann. Rev. Pharmacol. 15: 29–47, 1975.
 157. Kromer, W., U., Hollt, H. Schmidt, and A. Herz, Release of immunoreactive dynorphin from the isolated guinea‐pig small intestine is reduced during peristaltic activity. Neurosci. Lett. 25: 53–56, 1981.
 158. Kromer, W., and H. Schmidt, Opioids modulate intestinal peristalsis at a site of action additional to that modulating acetylcholine release. J. Pharmacol. Exp. Ther. 223: 271–274, 1982.
 159. Kromer, W., P., Schroder, and S. Netz, Stereospecific inhibition of naloxone of histamine‐stimulated acid secretion in isolated guinea pig parietal cells. Pharmacology 29: 320–328, 1984.
 160. Lamki, L., and S. Sullivan, A study of gastrointestinal opiate receptors: the role of mu receptor on gastric emptying: concise communication. J. Nucl. Med. 24: 689–692, 1983.
 161. Larsson, L. I., Corticotropin‐like peptides in central nerves and in endocrine cells of gut and pancreas. Lancet 2: 1321–1323, 1977.
 162. Larsson, L. I., ACTH‐like immunoreactivity in the gastrin cell. Independent changes in gastrin and ACTH‐like immunoreactivity during ontogeny. Histochemistry 56: 245–250, 1978.
 163. Larsson, L. I., Gastrin and ACTH‐like immunoreactivity occurs in two ultrastructurally distinct cell types of rat antropyloric mucosa. Evidence for a nonparallel processing of the peptides during feeding and fasting. Histochemistry 58: 33–40, 1978.
 164. Larsson, L. I., Radioimmunochemical characterization of ACTH‐like peptides in the antropyloric mucosa. Life Sci. 25: 1565–1572, 1978.
 165. Larsson, L. I., Distribution of ACTH‐like immunoreactivity in rat brain and gastrointestinal tract. Histochemistry 55: 225–228, 1978.
 166. Larsson, L. I., Innervation of the pancreas by substance P, enkephalin, vasoactive intestinal polypeptide and gastrin/CCK immunoreactive nerves. J. Histochem. Cytochem. 27: 1283–1284, 1979.
 167. Larsson, L. I., Simultaneous ultrastructural demonstration of multiple peptides in endocrine cells by a novel immunocytochemical method. Nature Lond. 282: 743–745, 1979.
 168. Larsson, L. I., Immunocytochemical characterization of ACTH‐like immunoreactivity in cerebral nerves and in endocrine cells of the pituitary and gastrointestinal tract by using region specific antisera. J. Histochem. Cytochem. 28: 133–140, 1980.
 169. Larsson, L. I., S., Childers, and S. H. Snyder, Met‐ and Leu‐enkephalin immune‐reactivity in separate neurons. Nature Lond. 282: 407–410, 1979.
 170. Larsson, L. I., and K. Stengaard‐Pedersen, Enkephalin/endorphin‐related peptides in antropyloric gastrin cells. J. Histochem. Cytochem. 29: 1088–1098, 1981.
 171. Larsson, L. I., and K. Stengaard‐Pedersen, Immunocytochemical and ultrastructural, differentiation between Met‐enkephalin, Leu‐enkephalin and Met/Leu‐enkephalin immunoreactive neurons of feline gut. J. Neurosci. 2: 861–878, 1982.
 172. Leander, S., R., Hakanson, and F. Sundler, Nerves containing substance P, vasoactive intestinal polypeptide, enkephalin or somatostatin in the guinea‐pig taenia coli. Cell Tissue Res. 215: 21–39, 1981.
 173. Linnoila, R. I., R. P., Diaugustine, R. J. Miller, K. J. Chang, and P. Cuatrecasas, An immunohistochemical and radioimmunological study of the distribution of Met5 and Leu5‐enkephalin in the gastrointestinal tract. Neuroscience 3: 1187–1196, 1978.
 174. Loukas, S., D., Varoucha, C. Zioudrou, R. A. Streaty, and W. A. Klee, Opioid activities and structures of α‐casein derived exorphins. Biochemistry 22: 4567–4573, 1983.
 175. Lundberg, J. M., T., Hökfelt, J. Kewenter, G. Pettersson, H. Ahlman, R. Edin, A. Dahlstrom, G. Nilsson, L. Terenius, K. Uvnas‐Wallensten, and S. Said, Substance P, VIP and enkephalin‐like immunoreactivity in the human vagus nerve. Gastroenterology 77: 468–471, 1979.
 176. Lundberg, J. M., T., Hökfelt, G. Nilsson, L. Terenius, J. Rehfeld, R. Elde, and S. Said, Peptide neurons in the vagus splanchnic and sciatic nerves. Acta Physiol. Scand. 104: 499–501, 1978.
 177. Lynch, D. R., and S. H. Snyder, Neuropeptides: multiple molecular forms, metabolic pathways and receptors. Annu. Rev. Biochem. 55: 773–799, 1986.
 178. Lynch, D. R., S. M., Strittmatter, and S. H. Snyder, Enkephalin convertase localization by [3H]guanidinoethylmercaptosuccinic acid autoradiography: selective association with enkephalin‐containing neurons. Proc. Natl. Acad. Sci. USA 81: 6543–6547, 1984.
 179. Macdonald, R. L., and M. A. Werz, Dynorphin A decreases voltage‐dependent calcium conductance of mouse dorsal root ganglion neurones. J. Physiol. Lond. 377: 237–249, 1986.
 180. Malfroy, B., J. P., Swerts, A. Guyon, B. P. Roques, and J. C. Schwartz, High‐affinity enkephalin‐degrading peptidase in brain is increased after morphine. Nature Lond. 276: 523–526, 1978.
 181. Malmfors, G., S., Leander, E. Brodin, R. Håkanson, T. Holmin, and F. Sundler, Peptide containing neurons intrinsic to the gut wall. Cell Tissue Res. 214: 225–238, 1981.
 182. Manara, L., G., Bianchi, P. Ferretto, E. Monferini, D. Strada, and A. Tavani, Local and CNS‐mediated effects of morphine and narcotic antagonists on gastrointestinal propulsion in rats. In: Endogenous and Exogenous Opiate Agonists and Antagonists, edited by E. Leong Way. New York: Pergamon, 1980, p. 143–146. (Proc. Int. Narcotic Research Club Conference, 11–15 June, 1979, North Falmouth, MA.)
 183. Manara, L., G., Bianchi, R. Fiocchi, A. Notarnicola, F. Peracchia, and A. Tavani, Inhibition of gastrointestinal transit by morphine and FK 33–824 in the rat and comparative narcotic antagonist properties of naloxone and its N‐methyl quaternary analog. Life Sci. 31: 1271–1274, 1982.
 184. Margolin, S., Centrally mediated inhibition of gastrointestinal propulsive motility by morphine over a non‐neural pathway. Proc. Soc. Exp. Biol. Med. 112: 311–315, 1963.
 185. Margolin, S., and O. J. Plekss, A neurohumoral substance discharged into blood perfusate from isolated rabbit heads by intracerebral morphine. Med. Pharmacol. Exp. 12: 1–8, 1965.
 186. Mass, C. L., Opiate antagonists stimulate ruminal motility of conscious goats. Eur. J. Pharmacol. 77: 71–74, 1982.
 187. Materia, A., B. M., Jaffe, I. M. Modlin, A. Sawk, and D. Albert, Effect of methionine‐enkephalin and naloxone on bombesin‐stimulated gastric acid secretion, gastrin and pancreatic polypeptide release in the dog. Ann. Surg. 196: 48–52, 1982.
 188. Matsuo, H., A., Miyata, and K. Mizuno, Novel C‐terminally amidated opioid peptide in human phaeochromocytoma tumour. Nature Lond. 305: 721–723, 1984.
 189. May, V., and B. A. Eipper, Regulation of peptide amidation in cultured pituitary cells. J. Biol. Chem. 260: 16224–16231, 1985.
 190. Mccallum, R. W., I., Doddo, H. P. Osborne, and P. Bianconi, Effect of enkephalin and other opiates on opossum lower esophageal sphincter. In: Gastrointestinal Motility, edited by J. Christensen. New York: Raven, 1980, p. 37–41.
 191. Mcgowan, A. M., W. L., Butsch, and W. Walters, Pressure in the common bile duct of man: its relation to pain following cholecystectomy. J. Am. Med. Assoc. 106: 2227–2230, 1936.
 192. Mcintosh, C. H. S., Y. W., Kwok, T. Morohorst, E. Nishmura, R. A. Pederson, and J. C. Brown, Enkephalinergic control of somatostatin secretion from the perfused rat stomach. Can. J. Physiol. Pharmacol. 61: 657–663, 1983.
 193. Mihara, S., and R. A. North, Opioids increase potassium conductance in guinea‐pig submucous neurones of guinea‐pig caecum by activating δ‐receptors. Br. J. Pharmacol. 88: 315–322, 1986.
 194. Mihara, S., and R. A. North, Receptors for dL‐opioids, α2‐agonists and somatostatin are coupled to the same potassium conductance in submucous plexus neurones. Br. J. Pharmacol. 87: 228p, 1986.
 195. Miller, R. J., Multiple opiate receptors for multiple opioid peptides. Med. Biol. 60: 1–6, 1982.
 196. Miller, R. J., The enkephalins. In: Handbook of Psychopharmacology, edited by L. L. Iversen, S. D. Iversen, and S. H. Snyder. New York: Plenum 1983, vol. 16, p. 107–207.
 197. Miller, R. J., The mucosa as a target tissue for gut neuropeptides. Trends Neurosci. 7: 2–3, 1984.
 198. Miller, R. J., Calcium channels in neurones. In: Receptor Biochemistry and Methodology. Structure and Physiology of the Slow Inward Calcium Channel, edited by D. J. Triggle and J. C. Venter. New York: Plenum, 1987, vol. 7, p. 161–246.
 199. Morita, K., and R. A. North, Opiate activation of potassium conductance on myenteric neurones: inhibition by calcium ions. Brain Res. 242: 145–150, 1981.
 200. Morley, J. E., A. S., Levine, and S. E. Silvus, Endogenous opiates and stress ulceration. Life Sci. 31: 693–699, 1982.
 201. Morley, J. E., A. S., Levine, and S. E. Silvus, Minireview: central regulation of gastric acid secretion: the role of neuropeptides. Life Sci. 31: 399–410, 1982.
 202. Morley, J. E., A. S., Levine, T. Yamada, W. F. Prigge, R. B. Shafer, F. C. Goetz, and S. E. Silvis, Effects of exorphins on gastrointestinal function, hormonal release, and appetite. Gastroenterology 84: 1517–1523, 1983.
 203. Mosberg, H. I., R., Hurst, V. J. Hruby, J. J. Galligan, T. F. Burks, K. Gee, and H. I. Yamamura, Conformationally constrained cyclic enkephalin analogs with pronounced δ‐opioid receptor agonist selectivity. Life Sci. 32: 2565–2569, 1983.
 204. Mosberg, H. I., R., Hurst, V. J. Hruby, K. Gee, H. I. Yamamura, J. J. Galligan, and T. F. Burks, Bis‐penicillamine enkephalins possess highly improved specificity toward δ‐opioid receptors. Proc. Natl. Acad. Sci. USA 80: 5871–5874, 1983.
 205. Nakanishi, S., A., Inoue, T. Kita, M. Nakamura, A. C. Y. Chang, S. N. Cohen, and S. Numa, Nucleotide sequence of cloned cDNA for bovine corticotropin/β‐lipotropin precursor. Nature Lond. 278: 423–427, 1979.
 206. Nihei, K., and T. Iwanaga, Localization of Met‐enkephalin‐Arg6‐Gly7‐Leu8‐like immunoreactivity in the gastrointestinal tract of rat and pig. J. Histochem. Cytochem. 33: 1001–1006, 1985.
 207. Nukamp, F. P., and J. M. Van Ree, Effects of endorphins on different parts of the gastrointestinal tract of rat and guinea pig in vitro. Br. J. Pharmacol. 68: 599–606, 1980.
 208. Nishi, R., and A. L. Willard, Neurons dissociated from rat plexus retain differentiated properties when grown in cell culture. I. Morphological properties and immunocytochemical localization of transmitter candidates. Neuroscience 16: 187–199, 1985.
 209. Nishimura, E., A. M. J., Buchan, and C. H. S. Mcintosh, Autoradiographic localization of opioid receptors in the rat stomach. Neurosci. Lett. 50: 73–78, 1984.
 210. Nishimura, S. L., L. D., Recht, and G. W. Pasternak, Biochemical characterization of high‐affinity 3H‐opioid binding. Further evidence for Mu1 sites. Mol. Pharmacol. 25: 29–37, 1984.
 211. Noda, M., Y., Furutani, H. Takahashi, M. Toyosato, T. Hirose, S. Inaguma, S. Nakanishi, and S. Numa, Cloning and sequence analysis of cDNA for bovine adrenal proenkephalin. Nature Lond. 295: 202–206, 1982.
 212. Norman, J. A., and J.‐Y. Chang, Proteolytic conversion of Met‐enkephalin‐Arg6‐Gly7‐Leu8 by brain synaptic membranes. J. Biol. Chem. 260: 2653–2656, 1985.
 213. North, R. A., Opioid receptor types and membrane ion channels. Trends Neurosci. 9: 114, 1986.
 214. North, R. A., Receptors in individual neurones. Neuroscience 17: 899–907, 1986.
 215. North, R. A., and J. T. Williams, Opiate activation of potassium conductance inhibits calcium action potentials in rat locus coeruleus neurones. Br. J. Pharmacol. 80: 225–228, 1983.
 216. North, R. A., and J. T. Williams, On the potassium conductance increased by opioids in rat locus coeruleus neurones. J. Physiol. Lond. 364: 265–280, 1985.
 217. Notarnicola, A., M., Landi, G. Bianchi, and A. Tawani, Relative ability of N‐methyl nalorphine and N‐methyl levallorphan to prevent antinociception and intestinal transit inhibition in morphine treated rats. Life Sci. 33: 481–484, 1983.
 218. Nowycky, M. C., A. D., Fox, and R. W. Tsien, Three types of neuronal calcium channel with different calcium agonist sensitivity. Nature Lond. 316: 440–443, 1985.
 219. Oka, K., J. D., Kantrowitz, and S. Spector, Isolation of morphine from toad skin. Proc. Natl. Acad. Sci. USA 82: 1852–1854, 1985.
 220. Oka, T., Enkephalin receptor in the rabbit ileum. Br. J. Pharmacol. 68: 193–195, 1980.
 221. Ooucm, M., H., Asaoka, T. Mitsutake, and M. Miyagawa, Endogenous opioid peptide effects on the guinea pig biliary tract. Peptides Fayetteville 4: 125–127, 1983.
 222. Orwoll, E. S., and J. W. Kendall, β‐Endorphin and adrenocorticotropin in extrapituitary sites: gastrointestinal tract. Endocrinology 107: 438–442, 1980.
 223. Parolaro, D., M., Sala, and E. Gori, Effect of intracerebroventricular administration of morphine upon intestinal motility in rat and its antagonism with naloxone. Eur. J. Pharmacol. 46: 329–338, 1977.
 224. Pascaud, X. B., M. G., Genton, G. Remond, and M. Vincent, Antral to colonic motility responses to intra cerebroventricular administrator of D‐ala‐2‐enkephalinamide, β‐endorphin, methionine enkephalin and fentanyl in anesthetized rats. In: Gastrointestinal Motility, edited by J. Christensen. New York: Raven, 1980, p. 459–466.
 225. Paterson, S. J., L. E., Robson, and H. W. Kosterlitz, Classification of opioid receptors. Br. Med. Bull. 39: 31–36, 1983.
 226. Paton, W. D. M., The action of morphine and related substances on contraction and on acetylcholine output of coaxially stimulated guinea‐pig ileum. Br. J. Pharmacol. 12: 119–127, 1957.
 227. Pederson, R. A., K. N., Kwok, A. M. J. Buchan, C. H. S. Mcintosh, and J. C. Brown, Gastrin release from isolated perfused rat stomach after vagotomy. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G248–G252, 1984.
 228. Peeters, T. L., G., Vantrappen, and J. Janssens, Fasting plasma motilin levels are related to the interdigestive motility complex. Gastroenterology 79: 716–724, 1980.
 229. Pert, C. B., and S. H. Snyder, Opiate receptor: demonstration in nervous tissue. Science Wash. DC 179: 1011–1014, 1973.
 230. Plant, O. H., and G. H. Miller, Effects of morphine and some other opium alkaloids on the muscular activity of the alimentary canal. I. Action on the small intestine in unanesthetized dogs and man. J. Pharmacol. Exp. Ther. 29: 361–383, 1926.
 231. Polak, J. M., S. R., Bloom, S. N. Sullivan, P. Facer, and A. G. E. Pearse, Enkephalin‐like immunoreactivity in the human gastrointestinal tract. Lancet 1: 972–974, 1977.
 232. Porreca, F., A., Cowan, R. B. Ratta, and R. J. Tallarida, Ketazocines and morphine: effects on gastrointestinal transit after central and peripheral administration. Life Sci. 32: 1785–1790, 1983.
 233. Porreca, F., H. I., Mosberg, R. Hurst, V. J. Hruby, and T. F. Burks, Roles of μ‐, δ‐, and κ‐opioid receptors in spinal and supraspinal mediation of gastrointestinal transit effects and hot‐plate analgesia in the mouse. J. Pharmacol. Exp. Ther. 230: 341–348, 1984.
 234. Powell, D. W., Muscle or mucosa: the site of action of antidiarrheal opiates? Gastroenterology 80: 406–408, 1981.
 235. Primi, M. P., L., Bueno, and J. Fioramonti, Central regulation of intestinal basal and stimulated water and ion transport by endogenous opioids in dogs. Dig. Dis. Sci. 31: 172–176, 1986.
 236. Probert, L., J., De May, and J. M. Polak, Ultrastructural localization of four different neuropeptides within separate populations of p‐type nerves in the guinea pig colon. Gastroenterology 85: 1094–1104, 1983.
 237. Pruitt, D. B., M. N., Grubb, D. L. Jaquette, and T. F. Burks, Intestinal effects of 5‐hydroxytryptamine and morphine in guinea pigs, dogs, cats and monkeys. Eur. J. Pharmacol. 26: 298–305, 1974.
 238. Radosevich, P. M., P. E., Williams, J. R. Mcrae, W. W. Lacey, D. N. Orth, and N. N. Abumrad, β‐endorphin inhibits glucose production in the conscious dog. J. Clin. Invest. 73: 1237–1241, 1984.
 239. Rattan, S., and R. J. Goyal, Identification and localization of opioid receptors in the opossum lower esophageal sphincter. J. Pharmacol. Exp. Ther. 224: 391–397, 1983.
 240. Rees, W. D. W., G. R., Sharpe, N. D. Christofides, S. R. Bloom, and L. A. Turnberg, The effects of an opiate agonist and antagonist on the human upper gastrointestinal tract. Eur. J. Clin. Invest. 13: 221–225, 1983.
 241. Reynolds, D. V., Surgery in the rat during electrical analgesia induced by focal brain stimulation. Science Wash. DC 164: 444–445, 1969.
 242. Reynolds, J. C., A., Ouyang, and S. Cohen, Evidence for an opiate‐mediated pyloric sphincter reflex. Am. J. Physiol. 246 Gastrointest. Liver Physiol. 9): G130–G136, 1983.
 243. Reynolds, J. C., A., Ouyang, and S. Cohen, Opiate nerves mediate feline pyloric response to intraduodenal amino acids. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G307–G312, 1985.
 244. Roques, B. P., M. C., Fournie‐Zaluski, E. Soroca, J. M. Malfroy, C. Malfroy, C. Llorens, and J. C. Schwartz, The enkephalinase inhibitor thiorphan shows antinociceptive activity in mice. Nature Lond. 288: 286–288, 1980.
 245. Roques, B. P., E., Lucas‐Soroca, P. Chaillet, J. Costentin, and M. C. Fournier‐Zaluski, Completed differentiation between enkephalinase and angiotensin‐converting enzyme inhibition by retro‐thiorphan. Proc. Natl. Acad. Sci. USA 80: 3178–3182, 1983.
 246. Rosenquist, G. L., K. Maruthainar, and D. G. Smyth, β‐Endorphin is present in active and inactive forms in rat gastric antrum. Biochem. Biophys. Res. Comm. 134: 14–20, 1986.
 247. Ruckebusch, Y., T. H., Bardon, and M. Pairet, Opioid control of the ruminant stomach motility: functional importance of μ‐, κ‐, and β‐receptors. Life Sci. 35: 1731–1738, 1984.
 248. Rudman, D., C. J., Berry, C. H. Riedenburg, B. M. Hollins, M. H. Kutner, M. J. Lynn, and R. K. Chawla, Effects of opioid peptides and opiate alkaloids on insulin secretion in the rabbit. Endocrinology 112: 1702–1710, 1983.
 249. Rzasa, P. J., K. V., Kaloustiom, and E. K. Prokop, Immunochemical evidence for Met‐enkephalin‐like and Leu‐enkephalin‐like peptides in tissues of the earthworm Lumbricus terrestris. Comp. Biochem. Biochem. Physiol. 776: 345–350, 1984.
 250. Saffrey, M. J., J. M., Polak, and G. Burnstock, Distribution of vasoactive intestinal polypeptide, substance P, enkephalin, and neurotensin‐like immunoreactive nerve fibers in the chicken gut during development. Neuroscience 7: 279–293, 1982.
 251. Sala, M., D., Parolaro, G. Crema, L. Spazzi, G. Gianoni, R. Cesana, and E. Gori, Involvement of periaquaductal gray matter in intestinal effect of centrally administered morphine. Eur. J. Pharmacol. 91: 251–254, 1983.
 252. Sarles, J. C., Hormonal control of the sphincter of Oddi. Dig. Dis. Sci. 31: 208–212, 1986.
 253. Sarna, S. K., Cyclic motor activity: migrating motor complex. Gastroenterology 89: 894–913, 1985.
 254. Sarna, S. K., W. Y., Chey, R. E. Condon, W. J. Dodds, T. Myers, and T‐M. Chang, Cause‐and‐effect relationship between motilin and migrating myoelectric complexes. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G277–G284, 1983.
 255. Sarna, S. K., R. E., Condon, and V. Cowles, Morphine versus motilin in the initiation of migrating myoelectric complexes. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G217–G222, 1983.
 256. Schaumann, W., Inhibition by morphine of the release of acetylcholine from the intestine of the guinea pig. Br. J. Pharmacol. 12: 115–119, 1957.
 257. Scheurer, U., E., Drack, and F. Halter, Cyclooxygenase inhibitors affect Met‐enkephalin and acetylcholine stimulated motility of the isolated rat colon. J. Pharmacol. Exp. Ther. 234: 742–746, 1985.
 258. Schiller, L. R., C. A. Santa, Ana, S. G. Morawski, and J. S. Fordtran, Mechanism of the antidiarrheal effect of loperamide. Gastroenterology 86: 1475–1480, 1984.
 259. Schultzberg, M., C. F., Dreyfus, M. D. Gershon, T. Hökfelt, R. P. Elde, G. Nilsson, S. Said, and M. Goldstein, VIP, enkephalin, substance P and somatostatin‐like immunoreactivity in neurons intrinsic to the intestine: immunohistochemical evidence from organotypic tissue cultures. Brain Res. 155: 239–248, 1978.
 260. Schultzberg, M., T., Hökfelt, G. Nilsson, L. Terenius, J. F. Rehfeld, M. Brown, R. Elde, M. Goldstein, and S. Said, Distribution of peptide‐ and catecholamine‐containing neurons in the gastro‐intestinal tract of rat and guinea‐pig: immunohistochemical studies with antisera to substance P, vasoactive intestinal polypeptide, enkephalins, somatostatin, gastrin/cholecystokinin, neurotensin and dopamine β‐hydroxylase. Neuroscience 5: 689–744, 1980.
 261. Schulz, R., M., Wuster, and A. Herz, Centrally and peripherally mediated inhibition of intestinal motility by opioids. Naunyn‐Schmiedebergs Arch Pharmacol. 308: 255–260, 1979.
 262. Schulz, R., M., Wuster, R. Simantov, S. H. Snyder, and A. Herz, Electrically stimulated release of opiate like material from the myenteric plexus of the guinea‐pig ileum. Eur. J. Pharmacol. 41: 347–348, 1977.
 263. Schusdziarra, V., A., Shick, A. De La Fuente, J. Specht, M. Klier, V. Brahtl, and E. F. Pfeiffer, Effect of β‐cosomorphins and analogs on insulin release in dogs. Endocrinology 112: 885–889, 1983.
 264. Schwartz, J. C., J., Costentin, and J. M. Lecomte, Pharmacology of enkephalinase inhibitors. Trends Pharmacol. Sci. 6: 471–477, 1985.
 265. Seizinger, B. R., C., Crimm, V. Holtt, and A. Herz, Evidence for a selective processing of proenkephalin B into different opioid peptide forms in particular regions of rat brain and pituitary. J. Neurochem. 42: 447–457, 1984.
 266. Seizinger, B. R., D. C., Liebisch, C. Gramsch, A. Herz, E. Weber, C. J. Evans, F. S. Esch, and P. Bohlen, Isolation and structure of a novel C‐terminally amidated opioid peptide, amidorphin, from bovine adrenal medulla. Nature Lond. 313: 57–59, 1985.
 267. Shea‐Donohue, P. T., N., Adams, J. Arnold, and A. Dubois, Effects of Met‐enkephalin and naloxone on gastric emptying and secretion in rhesus monkeys. Am. J. Physiol. 245 (Gastrointest. Liver Physiol. 8): G196–G200, 1983.
 268. Shimosegawa, T., S., Kobayashi, T. Fujita, T. Mochizuki, C. Yanaihara, and N. Tanaihara, Nerve elements containing Met‐enkephalin‐Arg6‐Gly7‐Leu8‐like immunoreactivity in canine pancreas a histochemical study. Neurosci. Lett. 42: 161–165, 1983.
 269. Simmonds, W. F., T. R., Burke, K. C. Rice, A. E. Jacobson, and W. A. Klee, Purification of the opiate receptor of NG108–15 neuroblastoma‐glioma hybrid cells. Proc. Natl. Acad. Sci. USA 82: 4974–4978, 1985.
 270. Simon, E. J., J. M., Hiller, and I. Edelman, Stereospecific binding of the potent narcotic analgesic [3H]etorphine to rat brain homogenate. Proc. Natl. Acad. Sci. USA 70: 1947–1949, 1973.
 271. Skov Olsen, P., P. Kirkegaard, B. Peterson, and J. Christiansen, Effect of naloxone on Met‐enkephalin induced acid secretion and serum gastrin in man. Gut 23: 63–65, 1982.
 272. Skov Olsen, P., P. Kirkegaard, B. Peterson, A. Lendorf, and J. Christiansen, The effect of a synthetic enkephalin analogue (FK 33–824) on gastric acid secretion and serum gastrin in man. Scand. J. Gastroenterol. 16: 531–533, 1981.
 273. Smith, T. W., J., Hughes, H. W. Kosterlitz, and R. P. Sosa, Enkephalins isolation, distribution and function. In: Opiates and Endogenous Opioid Peptides, edited by H. W. Kosterlitz. Amsterdam: Elsevier/North‐Holland, 1976, p. 57–61.
 274. Soll, A. H., Physiology of isolated canine parietal cells: receptors and effectors regulating function. In: Physiology of the Gastrointestinal Tract (1st ed.), edited by L. R. Johnson. New York: Raven, 1981, p. 673–692.
 275. Sosa, R. P., A. T., Mcknight, J. Hughes, and H. W. Kosterlitz, Incorporation of labelled amino acids into the enkephalins. FEBS Lett. 84: 1–8, 1977.
 276. Stacher, G., H., Steinringer, and G. Schmierer, Effects of the synthetic enkephalin analogue FK 33–824 on colonic motor activity in healthy man. In: Gastrointestinal Motility, edited by J. Christensen. New York: Raven, 1980, p. 443–450.
 277. Stern, A. S., R. V., Lewis, S. Kimura, J. Rossier, S. Stein, and S. Udenfriend, Opioid hexapeptides and heptapeptides in adrenal medulla and brain possible implications on the biosynthesis of enkephalins. Arch. Biochem. Biophys. 205: 606–613, 1980.
 278. Stern, A. S., R. J., Wurzburger, R. Barkey, and S. Spector, Opioid polypeptides in guinea pig pancreas. Proc. Natl. Acad. Sci. USA 79: 6703–6706, 1982.
 279. Stewart, J. J., Neostigmine antagonism of morphine's effects on intestinal transit. J. Pharm. Pharmacol. 34: 405–407, 1982.
 280. Stewart, J. J., N. W., Weisbrodt, and T. F. Burks, Changes in the myoelectric activity of the small intestine associated with drug‐induced emesis in the conscious cat. Proc. West. Pharmacol. Soc. 19: 439–444, 1976.
 281. Stewart, J. J., N. W., Weisbrodt, and T. F. Burks, Centrally mediated intestinal stimulation by morphine. J. Pharmacol. Exp. Ther. 202: 174–181, 1977.
 282. Stewart, J. J., N. W., Weisbrodt, and T. F. Burks, Central and peripheral actions of morphine on intestinal transit. J. Pharmacol. Exp. Ther. 205: 547–555, 1978.
 283. Strittmatter, S. M., D. R., Lynch, and S. H. Snyder, [3H]guanidinoethylmercaptosuccinic acid binding to tissue homogenates. Selective labeling of enkephalin convertase. J. Biol. Chem. 259: 11812–11817, 1984.
 284. Sullivan, S. N., M., Corke, and R. Darwish, Inhibition of basal and stimulated gastrin acid secretion by an enkephalin analogue. Am. J. Gastroenterol. 77: 360–362, 1982.
 285. Sundler, F., J., Alumets, R. Ekman, R. Håkanson, and T. B. VanWimersma Greidanus, Immunoreactive adrenocorticotropic hormone (ACTH) in porcine gut and pancreas: fact or artifact? J. Histochem. Cytochem. 29: 1328–1335, 1981.
 286. Sundler, F., J., Alumets, and R. Håkanson, ACTH in porcine gut and pancreas: fact or artifact? Regul. Pept. Suppl. 1: 111, 1980.
 287. Surprenant, A., and R. A. North, μ‐Opioid receptors and α2‐adrenoceptors co‐exist on myenteric but not on submucous neurones. Neuroscience 16: 425–430, 1985.
 288. Szerb, J. C., Correlation between acetylcholine release and activity in the guinea‐pig ileum myenteric plexus; effect of morphine. Neuroscience 7: 327–340, 1982.
 289. Tachibana, S., K., Araki, S. Ohya, and Y. Yoshida, Isolation and structure of dynorphin, an opioid peptide, from porcine duodenum. Nature Lond. 295: 339–340, 1982.
 290. Tahara, E., K., Tanaka, and A. Miyoshi, β‐Endorphin‐like immunoreactivity and somatostatin‐like immunoreactivity in normal gastric mucosa, muscle layer, and adenocarcinoma. Gastroenterology 88: 670–674, 1985.
 291. Tanaka, I., Y., Nakai, N. Kazuwa, N. Shogo, S. Oki, N. Masaki, I. T. Ohtsuki, and H. Imura, Presence of immunoreactive α‐melanocyte hormone, adrenocorticotropin and β‐endorphin in human gastric antral mucosa. J. Clin. Endocrinol. Metab. 54: 392–397, 1982.
 292. Tang, J., H.‐Y., Yang, and E. Costa, Distribution of Met5‐enkephalin‐Arg6‐Phe7 (MEAD) in various tissues of rats and guinea‐pigs. Life Sci. 31: 2303–2306, 1982.
 293. Tari, A., Y., Miyachi, M. Hide, K. Sumii, G. Kajiyama, E. Tahara, K. Tanaka, and A. Miyoshi, β‐Endorphin‐like immunoreactivity and somatostatinlike immunoreactivity in normal gastric mucosa, muscle layer, and adenocarcinoma. Gastroenterology 88: 670–674, 1985.
 294. Tavani, A., G., Bianchi, P. Ferritti, and L. Manara, Morphine is most effective on gastrointestinal propulsion in rats by intraperitoneal route: evidence for local action. Life Sci. 27: 2211–2217, 1980.
 295. Telford, G. H., M., Hoshmonai, A. J. Moses, and J. H. Szurszewski, Morphine initiates migrating myoelectric complexes by acting on peripheral opioid receptors. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G557–G562, 1985.
 296. Telford, G. H., and J. H. Szurszewski, Blockade of migrating myoelectric complexes by naloxone (Abstract). Gastroenterology 86: 1278, 1984.
 297. Terenius, L., Stereospecific interaction between a narcotic analgesic and a synaptic plasma membrane fraction in rat brain. Acta Pharmacol. Toxicol. 33: 377–384, 1973.
 298. Teschemacher, H., K. E., Opheim, B. M. Cox, and A. Goldstein, A peptide like substance from the pituitary that acts like morphine. I. Isolation. Life Sci. 16: 1771–1775, 1976.
 299. Trendelenburg, P., Physiologische und pharmakologische Versuche uber die Dunndarmperistaltik. Arch. Exp. Pathol. Pharmakol. 81: 55–129, 1917.
 300. Turner, A. J., J., Hryszko, and N. W. Bunnett, Endopeptidase‐24.11 (enkephalinase) from porcine fundic muscle: purification and characterization (Abstract). Regul. Pept. 13: 72, 1985.
 301. Uddman, R., J., Alumets, R. Håkanson, F. Sundler, and B. Wallus, Peptidergic (enkephalin) innervation of the mammalian esophagus. Gastroenterology 78: 732–737, 1980.
 302. Van Noorden, S., and S. Falkmer, Gut‐islet endocrinology‐some evolutionary aspects. Invest. Cell Pathol. 3: 21–35, 1982.
 303. Vantrappen, G., J., Janssens, T. L. Peeters, S. R. Bloom, N. D. Christofides, and J. Hellemans, Motilin and the interdigestive migrating motor complex in man. Dig. Dis. Sci. 24: 497–500, 1979.
 304. Vaughan Williams, E. M., The model of action of drugs upon intestinal motility. Pharmacol. Rev. 6: 159–190, 1954.
 305. Vaught, J. L., A., Cowan, and H. I. Jacoby, μ‐ And δ‐, but not κ‐opioid agonists induce contractions of the canine small intestine in vivo. Eur. J. Pharmacol. 109: 43–48, 1985.
 306. Vincent, S. R., C.‐J., Dalsgaard, M. Schultzberg, T. Hökfelt, I. Christensson, and L. Terenius, Dynorphin‐immunoreactive neurons in the autonomic nervous system. Neuroscience 11: 973–987, 1984.
 307. Vizi, E. S., K., Oao, V. Adam‐Vizi, D. Duncalf, and F. F. Foldes, Presynaptic inhibitory effect of Met‐enkephalin on 14C acetylcholine release from the myenteric plexus and its interaction with muscarinic negative feedback inhibition. J. Pharmacol. Exp. Ther. 230: 493–499, 1984.
 308. Vuolteenano, O., O., Vakkuri, and J. Leppaluoto, Wide distribution of β‐endorphin‐like immunoreactivity in extrapituitary tissues of rat. Life Sci. 27: 57–65, 1980.
 309. Wang, Y.‐N., A. C., Church, and R. J. Wyatt, Localization of Met5‐immunoreactivity in the rat gastrointestinal tract. Neuroscience 51: 319–324, 1984.
 310. Ward, S. J., and A. E. Takemori, Relative involvement of receptor subtypes in opioid‐induced inhibition of gastrointestinal transit in mice. J. Pharmacol. Exp. Ther. 224: 359–363, 1983.
 311. Watson, S. J., H., Akil, E. Ghazarossian, and A. Goldstein, Dynorphin immunocytochemical localization in brain and peripheral nervous system: preliminary studies. Proc. Natl. Acad. Sci. USA 78: 1260–1263, 1981.
 312. Weber, E., F. S., Esch, P. Bohlen, A. D. Corbett, A. T. Mcknight, H. W. Kosterlitz, J. D. Borchus, and C. J. Evans, Metorphamide: isolation structure and biologic activity of an amidated opioid octapeptide from bovine brain. Proc. Natl. Acad. Sci. USA 80: 7362–7366, 1983.
 313. Weber, E., C. J., Evans, and J. D. Barchas, Predominance of the amino‐terminal octapeptide fragment of dynorphin in rat brain regions. Nature Lond. 299: 77–79, 1982.
 314. Weinstock, M., Peripheral tissues. In: Narcotic Drugs Biochemical Pharmacology, edited by D. H. Clouet. New York: Plenum, 1971, p. 394–401.
 315. Weisbrodt, N. W., S. E., Sussman, J. J. Stewart, and T. F. Burks, Effect of morphine sulfate on intestinal transit and myoelectric activity of the small intestine of the rat. J. Pharmacol. Exp. Ther. 214: 333–338, 1980.
 316. Weisbrodt, N. W., P. J., Thor, J. Anderson, and E. M. Copeland, Morphines effect on intestinal motility is mediated via the central nervous system. In: Motility of the Digestive Tract, edited by M. Weinbeck. New York: Raven, 1982, p. 461–466.
 317. Werther, G. A., S., Joffe, R. Artal, and M. A. Sperling, Opiates modulate insulin action in vivo in dogs. Diabetologia 26: 65–69, 1984.
 318. Werz, M. A., and R. L. Macdonald, Opioid peptides selective for μ‐ and δ‐opiate receptors reduce calcium‐dependent action potential duration by increasing potassium conductance. Neurosci. Lett. 42: 173–178, 1983.
 319. Werz, M. A., and R. L. Macdonald, Opioid peptides with differential affinity for mu and delta receptors decrease sensory neuron calcium‐dependent action potentials. J. Pharmacol. Exp. Ther. 227: 394–402, 1983.
 320. Werz, M. A., and R. L. Macdonald, Dynorphin reduces calcium‐dependent action potential duration by decreasing voltage‐dependent calcium conductance. Neurosci. Lett. 46: 185–190, 1984.
 321. Werz, M. A., and R. L. Macdonald, Dynorphin reduces voltage‐dependent calcium conductance of mouse dorsal root ganglion neurones. Neuropeptides 5: 253–256, 1984.
 322. Werz, M. A., and R. L. Macdonald, Dynorphin and neoendorphin peptides decrease dorsal root ganglion neuron calcium‐dependent action potential duration. J. Pharmacol. Exp. Ther. 234: 49–56, 1985.
 323. Williams, R. G., and G. J. Dockray, Distribution of enkephalin‐related peptides in rat brain: immunohistochemical studies using antisera to Met5‐enkephalin and Met5‐enke‐phalin‐Arg6‐Phe7. Neuroscience 9: 563–571, 1983.
 324. Wolter, H. J., Adrenocorticotropin and β‐endorphin are co‐localized in the nervous system of rat duodenum. Biochem. Biophys. Res. Commun. 117: 569–573, 1983.
 325. Wolter, H. J., α‐Melanotropin and β‐endorphin‐like immunoreactivities are contained within neurons and nerve fibers of the rat duodenum. Brain Res. 295: 378–384, 1984.
 326. Wolter, H. J., Ultrastructural evidence for β‐endorphin‐like reactivity in the nervous system of the rat duodenum. Brain Res. 334: 194–199, 1985.
 327. Wolter, H. J., Corticotropin‐release factor: immunohistochemical co‐localization with adrenocorticotropin and β‐endorphin, but not with Met‐enkephalin, in subpopulations of duodenal perikarya or rat. Biochem. Biophys. Res. Commun. 228: 402–410, 1985.
 328. Wolter, H. J., Co‐localization of dynorphin‐A‐(1–17) and dynorphin‐A‐(1–8) within some perikarya of rat duodenum: immunohistochemical evidence for the presence of two separate dynorphinergic systems. Biochem. Biophys. Res. Commun. 130: 774–780, 1985.
 329. Wolter, H. J. Dynorphin‐A‐(1–8) is contained within perikarya, nerve fibers and nerve terminals of rat duodenum. Biochem. Biophys. Res. Commun. 127: 610–625, 1985.
 330. Wood, P. L., Multiple opiate receptors: support for unique μ‐, δ‐, and κ‐site. Neuropharmacology 21: 487–497, 1982.
 331. Wood, S. M., J. M., Polak, and S. R. Bloom, Neuropeptides in the control of the islets of Langerhans. Adv. Metab. Disord. 10: 401–419, 1983.
 332. Worobetz, L. J., R. J., Baker, J. A. Mccallum, G. Wells, and S. N. Sullivan, The effect of naloxone, morphine and an enkephalin analogue on cholecystokinin octapeptide‐stimulated gallbladder emptying. Am. J. Gastroenterol. 77: 509–511, 1982.
 333. Wuster, M., R., Schulz, and A. Herz, Multiple opiate receptors in peripheral tissue preparations. Biochem. Pharmacol. 30: 1883–1887, 1981.
 334. Yamada, J., and W. J. Krause, An immunohistochemical survey of endocrine cells and nerves in the proximal small intestine of the platypus, Ornithorhynchus anatinus. Cell Tissue Res. 234: 153–164, 1983.
 335. You, C. H., W. Y., Chey, and K. Y. Lee, Studies on plasma motilin concentration and interdigestive motility of the duodenum in humans. Gastroenterology 79: 62–69, 1980.
 336. Zamir, N., M., Palkovits, and M. J. Brownstein, The distribution of immunoreactive α‐neo‐endorphin in the central nervous system of the rat. J. Neurosci. 4: 1240–1247, 1984.
 337. Zamir, N., M., Palkovits, F. Mezuy, and M. J. Brownstein, A dynorphinergic pathway of Leu‐enkephalin production in rat substantia nigra. Nature Lond. 307: 642–645, 1984.
 338. Zamir, N., E., Weber, M. Palkovits, and M. J. Brownstein, Differential processing of prodynorphin and proenkephalin in specific regions of the rat brain. Proc. Natl. Acad. Sci. USA 81: 6886–6889, 1984.
 339. Zukin, R. S., and S. R. Zukin, The case for multiple opiate receptors. Trends Neurosci. 7: 160–164, 1984.

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Article Title: Opioid Peptides of The Gut
 

How to Cite

Richard J. Miller, Lane D. Hirning. Opioid Peptides of The Gut. Compr Physiol 2011, Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology: 631-660. First published in print 1989. doi: 10.1002/cphy.cp060226