Comprehensive Physiology Wiley Online Library
For Librarians For Authors Editors About

Gastrin

G. J. Dockray, R. A. Gregory

10.1002/cphy.cp060215

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 Unequivocal Identification of a Pyloric Antral Hormone
2 Isolation and Characterization of Tissue Forms and Fragments
2.1 Heptadecapeptide (Little) Gastrin: G‐17
2.2 Big Gastrin: G‐34
2.3 Minigastrin: G‐14
2.4 Small Cooh‐Terminal Fragments of G‐17
2.5 Biologically Inactive Forms and Fragments
3 Molecular Biology—Biosynthesis
4 Distribution
4.1 Identification of Gastrin Cells
4.2 Phylogeny
4.3 Ontogeny
4.4 Regulation of G Cell Numbers
5 Measurement by Radioimmunoassay
5.1 Antibodies
5.2 Plasma Forms
5.3 Gastrin in Antral Venous Outflow: Postsecretory Processing
6 Metabolism
7 Release
7.1 Luminal Mechanisms
7.2 Hormonal and Paracrine Effects
7.3 Nervous Control
8 Actions of Gastrin
8.1 Trophic Actions
9 Structure‐Function Relationships
9.1 Cooh‐Terminal Fragments
9.2 Other Gastrin Fragments
9.3 Antagonists
10 Receptors
Figure 1. Figure 1.

Amino acid sequences for little gastrins from antrum of 8 mammalian species. A space indicates a residue identical to that in human G‐17. Tyrosine occurs in both sulfated and unsulfated forms. Little gastrins are heptadecapeptides, with the exception of guinea pig gastrin, which is a hexadecapeptide in which one Glu is deleted (arbitrarily identified here by ×).
Figure 2. Figure 2.

Amino acid sequence of human and porcine gastrin precursors deduced from cDNA sequencing. Porcine precursor is 104 residues; human precursor is 101 residues. Both contain a signal sequence of ˜21 residues that is rapidly removed. Box, sequence corresponding to G‐34; arrowheads, cleavage sites. A space indicates a residue identical with that above.
Figure 3. Figure 3.

Schematic representation of biosynthetic processing pathway of progastrin in antral mucosa. Cleavage at pairs of basic residues (→) liberates an NH2‐terminal flanking peptide (cryptic A), the NH2‐terminal tryptic peptide of G‐34 (NTG34), G‐17 (after amidation of the COOH‐terminal Phe residue), and a COOH‐terminal flanking peptide (cryptic B). Relatively high concentrations of G‐34 in human duodenum suggest that there are cell‐specific patterns of processing.
Figure 4. Figure 4.

Time courses of plasma G‐17 and G‐34 responses to feeding in humans. Heptadecapeptide was estimated by radioimmunoassay with a specific antiserum, and G‐34 was estimated by subtraction of G‐17 from total COOH‐terminal immunoreactivity; a small amount of G‐14 will also be included in this fraction.

From Dockray and Taylor 52), © by Williams & Wilkins, 1976
Figure 5. Figure 5.

Separation on Sephadex G‐50 of an antral extract and of plasma taken from the antral venous outflow of dog. Two antibodies were used in radioimmunoassays; one is specific for the COOH‐terminus of G‐17 (•), the other for intact G‐17 (○). Material with immunochemical and chromatographic properties of G‐17 predominates in antral tissue extracts, but in the antral venous outflow, COOH‐terminal immunoreactive fragments, probably G‐16 and G‐14, predominate. [Adapted from Dockray et al. 51).]
Figure 6. Figure 6.

Metabolism of unsulfated G‐17 in humans. Chromatographic separation on diethylaminoethyl cellulose of immunoreactive gastrin in plasma measured by antibodies specific for the NH2‐terminus of G‐17 (Δ), COOH‐terminus of G‐17 (•), and intact G‐17 (○). At a steady state during infusion of G‐17, the intact peptide is found in plasma, together with peaks corresponding to G‐14, and 2 NH2‐ter‐minal fragments, one of which may be 1–13 G‐17; the latter fragments have a longer half‐life and so account for a progressively greater proportion of total plasma immunoreactivity after stopping the infusion.

From Pauwels et al. 181
Figure 7. Figure 7.

COOH‐terminal immunoreactivity in dog plasma showing differences between feeding, instilling a test meal directly into the gastric fistula, and the effect in each case of titrating intragastric pH to 6.0. Note prompt plasma response to feeding, sluggish response to intragastric instillation of the meal, and effect of acid inhibition.

From Dockray and Tracy 53
Figure 8. Figure 8.

Time course of acid secretion to G‐17 and G‐34 in humans, in response to equimolar doses. Note higher peaks and longer response to G‐34 due to its longer half‐life.

From Eysselein et al. 71


Figure 1.

Amino acid sequences for little gastrins from antrum of 8 mammalian species. A space indicates a residue identical to that in human G‐17. Tyrosine occurs in both sulfated and unsulfated forms. Little gastrins are heptadecapeptides, with the exception of guinea pig gastrin, which is a hexadecapeptide in which one Glu is deleted (arbitrarily identified here by ×).



Figure 2.

Amino acid sequence of human and porcine gastrin precursors deduced from cDNA sequencing. Porcine precursor is 104 residues; human precursor is 101 residues. Both contain a signal sequence of ˜21 residues that is rapidly removed. Box, sequence corresponding to G‐34; arrowheads, cleavage sites. A space indicates a residue identical with that above.



Figure 3.

Schematic representation of biosynthetic processing pathway of progastrin in antral mucosa. Cleavage at pairs of basic residues (→) liberates an NH2‐terminal flanking peptide (cryptic A), the NH2‐terminal tryptic peptide of G‐34 (NTG34), G‐17 (after amidation of the COOH‐terminal Phe residue), and a COOH‐terminal flanking peptide (cryptic B). Relatively high concentrations of G‐34 in human duodenum suggest that there are cell‐specific patterns of processing.



Figure 4.

Time courses of plasma G‐17 and G‐34 responses to feeding in humans. Heptadecapeptide was estimated by radioimmunoassay with a specific antiserum, and G‐34 was estimated by subtraction of G‐17 from total COOH‐terminal immunoreactivity; a small amount of G‐14 will also be included in this fraction.

From Dockray and Taylor 52), © by Williams & Wilkins, 1976


Figure 5.

Separation on Sephadex G‐50 of an antral extract and of plasma taken from the antral venous outflow of dog. Two antibodies were used in radioimmunoassays; one is specific for the COOH‐terminus of G‐17 (•), the other for intact G‐17 (○). Material with immunochemical and chromatographic properties of G‐17 predominates in antral tissue extracts, but in the antral venous outflow, COOH‐terminal immunoreactive fragments, probably G‐16 and G‐14, predominate. [Adapted from Dockray et al. 51).]



Figure 6.

Metabolism of unsulfated G‐17 in humans. Chromatographic separation on diethylaminoethyl cellulose of immunoreactive gastrin in plasma measured by antibodies specific for the NH2‐terminus of G‐17 (Δ), COOH‐terminus of G‐17 (•), and intact G‐17 (○). At a steady state during infusion of G‐17, the intact peptide is found in plasma, together with peaks corresponding to G‐14, and 2 NH2‐ter‐minal fragments, one of which may be 1–13 G‐17; the latter fragments have a longer half‐life and so account for a progressively greater proportion of total plasma immunoreactivity after stopping the infusion.

From Pauwels et al. 181


Figure 7.

COOH‐terminal immunoreactivity in dog plasma showing differences between feeding, instilling a test meal directly into the gastric fistula, and the effect in each case of titrating intragastric pH to 6.0. Note prompt plasma response to feeding, sluggish response to intragastric instillation of the meal, and effect of acid inhibition.

From Dockray and Tracy 53


Figure 8.

Time course of acid secretion to G‐17 and G‐34 in humans, in response to equimolar doses. Note higher peaks and longer response to G‐34 due to its longer half‐life.

From Eysselein et al. 71
References
 1. Alumets, J., H. A. El, Munshid, R. Håkanson, J. Hedenbro, G. Liedberg, J. Oscarson, J. F. Rehfeld, F. Sundler, and S. Vallgren. Gastrin cell proliferation after chronic stimulation: effect of vagal denervation or gastric surgery in the rat. J. Physiol. Lond. 298: 557–569, 1980.
 2. Babkin, B. P. Die äussere Sekretion der Verdauungsdrüsen (2nd ed.). Berlin: Springer‐Verlag, 1928.
 3. Barger, G., and H. H. Dale. β‐Iminazolylethylamine a depressor constituent of intestinal mucosa. J. Physiol. Lond. 41: 499–503, 1910.
 4. Baur, S., and V. C. Bacon. A specific gastrin receptor on plasma membranes of antral smooth muscle. Biochem. Biophys. Res. Commun. 73: 928–933, 1976.
 5. Bayliss, W. M., and E. H. Starling. The mechanism of pancreatic secretion. J. Physiol. Lond. 28: 325–353, 1902.
 6. Berson, S. A., and R. S. Yalow. Nature of immunoreactive gastrin extracted from tissues of gastrointestinal tract. Gastroenterology 60: 215–222, 1971.
 7. Bertaccini, G., V., Erspamer, P. Melchiorri, and N. So‐Pranzi. Gastrin release by bombesin in the dog. Br. J. Pharmacol. 52: 219–225, 1974.
 8. Bertrand, P., and G. Willems. Induction of antral gastrin cell proliferation by refeeding of rats after fasting. Gastroenterology 78: 918–924, 1980.
 9. Blair, E. L., E. R., Grund, P. K. Lund, A. Piercy, J. D. Reed, D. J. Sanders, D. Shale, B. Shaw, and J. Wilkinson. Comparison of vagal and meat stimulation on gastric acid secretion and serum gastrin. J. Physiol. Lond. 266: 157–172, 1977.
 10. Blair, E. L., E. R., Grund, P. K. Lund, and D. J. Sanders. A possible origin of circulating gastrin component IV in cats. J. Physiol. Lond. 273: 561–572, 1977.
 11. Bloom, S. R., C. H., Mortimer, M. O. Thorner, G. M. Besser, R. Hall, A. Gomez‐Pan, V. M. Roy, R. C. G. Russell, D. H. Coy, A. J. Kastin, and A. V. Schally. Inhibition of gastrin and gastric‐acid secretion by growth‐hormone release inhibiting hormone. Lancet 2: 1106–1109, 1974.
 12. Boel, E., J., Vuust, F. Norris, K. Norms, A. Wind, J. F. Rehfeld, and K. A. Marcker. Molecular cloning of human gastrin cDNA: evidence for evolution of gastrin by gene duplication. Proc. Natl. Acad. Sci. USA 80: 2866–2869, 1983.
 13. Bonato, C., J., Eng, Y.‐C. E. Pan, M. Chang, J. D. Hulmes, and R. Yalow. Guinea pig little gastrin is a hexadecapeptide (Abstract). Gastroenterology 88: 1330, 1985.
 14. Boniface, J., D., Picone, M. Schebalin, A. M. Zfass, and G. M. Makhlouf. Clearance rate, half‐life, and secretory potency of human gastrin‐17‐I in different species. Gastroenterology 71: 291–294, 1976.
 15. Bradbury, A. F., M. D. A., Finnie, and D. G. Smyth. Mechanism of C‐terminal amide formation by pituitary enzymes. Nature Lond. 298: 636–638, 1982.
 16. Brand, S. J., B. N., Andersen, and J. F. Rehfeld. Complete tyrosine‐O‐sulphation of gastrin in neonatal rat pancreas. Nature Lond. 309: 456–458, 1984.
 17. Brand, S. J., J., Klarlund, T. W. Schwartz, and J. F. Rehfeld. Biosynthesis of tyrosine O‐sulphated gastrins in rat antral mucosa. J. Biol. Chem. 259: 13246–13252, 1984.
 18. Brandsborg, O., M., Brandsborg, and N. J. Christensen. Plasma adrenaline and serum gastrin: studies in insulin‐induced hypoglycemia and after adrenaline infusions. Gastroenterology 68: 455–460, 1975.
 19. Brandsborg, O., M., Brandsborg, and N. J. Christensen. The role of the β‐adrenergic receptor in stimulation of gastrin: studies in normal subjects and in patients with duodenal ulcer. Eur. J. Clin. Invest. 6: 202–206, 1978.
 20. Brodin, K., and G. Nilsson. Increase in duodenal tissue gastrin in dogs following antrectomy with gastroduodenostomy and after total gastrectomy with oesophagoduodenostomy. Acta Physiol Scand. 116: 113–120, 1982.
 21. Brown, J., and N. D. Gallagher. A specific gastrin receptor site in the rat stomach. Biochim. Biophys. Acta 538: 42–49, 1978.
 22. Buchan, A. M. J., J. M., Polak, E. Solcia, and A. G. E. Pearse. Localisation of intestinal gastrin in a distinct endocrine cell type. Nature Lond. 277: 138–140, 1979.
 23. Buffa, R., I., Solovieva, R. Fiocca, S. Giorgino, G. Rindi, E. Solcia, T. Mochizuchi, C. Yanaihara, and N. Yanaihara. Localization of bombesin and GRP (gastrin releasing peptide) sequences in gut nerves or endocrine cells. Histochemistry 76: 457–467, 1982.
 24. Calam, J., G. J., Dockray, R. Walker, H. J. Tracy, and D. Owens. Molecular forms of gastrin in peptic ulcer: comparison of serum and tissue concentrations of G17 and G34 in gastric and duodenal ulcer subjects. Eur. J. Clin. Invest. 10: 241–247, 1980.
 25. Cantor, P., and J. F. Rehfeld. The molecular nature of cholecystokinin in the feline pancreas and related nervous structures. Regul. Pep. 8: 199–208, 1984.
 26. Carter, D. C., I. L., Taylor, J. Elashoff, and M. I. Grossman. Reappraisal of the secretory potency and disappearance rate of pure human minigastrin. Gut 20: 705–708, 1979.
 27. Chew, C. S., and S. J. Hersey. Gastrin stimulation of isolated gastric glands. Am. J. Physiol. 242 (Gastrointest. Liver Physiol. 5): G504–G512, 1982.
 28. Chiba, T., T., Taminato, S. Kadowaki, H. Abf, K. Chihara, Y. Seino, S. Matsukura, and T. Fujita. Effects of glucagon, secretin and vasoactive intestinal polypeptide on gastric somatostatin and gastrin release from isolated perfused rat stomach. Gastroenterology 79: 67–71, 1980.
 29. Christiansen, L. A. The metabolism of gastrin‐34, gastrin‐17, and gastrin‐14 in the isolated perfused pig liver. Scand. J. Gastroenterol. 19: 131–138, 1984.
 30. Clendinnen, B. G., W. D., Davidson, D. D. Reeder, B. M. Jackson, and J. C. Thompson. Renal uptake and excretion of gastrin in the dog. Surg. Gynecol. Obstet. 132: 1039–1043, 1971.
 31. Crean, G. P., R. D. E., Rumsey, D. F. Hogg, and M. W. Marshall. Experimental hyperplasia of the gastric mucosa. In: Physiology of Gastric Secretion, edited by L. S. Semb and J. Myren, Baltimore, MD: Williams & Wilkins, 1968.
 32. Dale, H. H., and P. P. Laidlaw. The physiological action of β‐iminazolylethylamine. J. Physiol. Lond. 41: 318–344, 1910.
 33. Davidson, W. D., T. C., Moore, W. Shippey, and A. J. Conovaloff. Effect of bilateral nephrectomy and bilateral ureteral ligation on serum gastrin levels in the rat. Gastroenterology 66: 522–525, 1974.
 34. Davidson, W. D., P. D., Springberg, and N. R. Falkinburg. Renal extraction and excretion of endogenous gastrin in the dog. Gastroenterology 64: 955–961, 1973.
 35. Debas, H. T., A., Csendes, J. H. Walsh, and M. I. Grossman. Release of antral gastrin. In: Endocrinology of the Gut, edited by W. Y. Chey and F. P. Brooks. Thorofare, NJ: Slack, 1974, p. 222–232.
 36. Debas, H. T., J., Hollinshead, A. Seal, P. Soon‐Shiong, and J. H. Walsh. Vagal control of gastrin release in the dog: pathways for stimulation and inhibition. Surgery St. Louis 95: 34–37, 1984.
 37. Debas, H. T., J. H., Walsh, and M. I. Grossman. Evidence for oxyntopyloric reflex for release of antral gastrin. Gastroenterology 68: 687–690, 1975.
 38. Debas, H. T., J. H., Walsh, and M. I. Grossman. After vagotomy atropine suppresses gastrin release by food. Gastroenterology 70: 1082–1084, 1976.
 39. Desmond, H. P., G. J., Dockray, and M. Spurdens. Identification by specific radioimmunoassay of two novel peptides derived from the C‐terminus of porcine preprogastrin. Regul. Pept. 11: 133–142, 1985.
 40. Desmond, H., S. Pauwels, A. Varro, H. Gregory, J. Young, and G. J. Dockray. Isolation and characterization of the intact gastrin precursor from a gastrinoma. FEBS Lett. 210: 185–188, 1987.
 41. Dimaline, R. Isolation and characterization of gastrin related peptides from the chicken (Abstract). Dig. Dis. Sci. 29, Suppl.: 22S, 1984.
 42. Dimaline, R., B. B., Rawdon, S. Brandes, A. Andrew, and J. P. Loveridge. Biologically active gastrin/CCK‐related peptides in the stomach of a reptile, Crocodylus niloticus; identified and characterized by immunochemical methods. Peptides Fayetteville 3: 977–984, 1982.
 43. Dimaline, R., J. Young, and H. Gregory. Isolation from chicken antrum, and primary amino acid sequence of a novel 36‐residue peptide of the gastrin/CCK family. FEBS Lett. 205: 318–322, 1986.
 44. Dockray, G. J. Immunochemistry of gastrin and cholecystokinin: development and application of region specific antisera. In: Gastrins and the Vagus, edited by J. F. Rehfeld and E. Amdrup. London: Academic, 1979, p. 73–83.
 45. Dockray, G. J. Immunochemical studies on big gastrin using NH2‐terminal specific antisera. Regul. Pept. 1: 169–186, 1980.
 46. Dockray, G. J. Cholecystokinin. In: Brain Peptides, edited by D. T. Krieger, M. J. Brownstein, and J. B. Martin. New York: Wiley, 1983, p. 851–869.
 47. Dockray, G. J., L., Best, and I. L. Taylor. Immunochemical characterization of gastrin in pancreatic islets of normal and genetically obese mice. J. Endocrinol. 72: 143–151, 1977.
 48. Dockray, G. J., and R. Dimaline. Evolution of the gastrin/CCK family. In: Evolution and Tumour Pathology of the Neuroendocrine System, edited by S. Falkmer, R. Håkanson, and F. Sundler. Amsterdam: Elsevier, 1984, p. 313–333.
 49. Dockray, G. J., and R. A. Gregory. Does the C‐terminal tetrapeptide of gastrin and CCK exist as an entity? Nature Lond. 286: 742, 1980.
 50. Dockray, G. J., R. A., Gregory, L. Hood, and M. Hunkapiller. NH2‐terminal dodecapeptide of porcine big gastrin: revised sequence and confirmation of structure by immunochemical analysis. Bioorg. Chem. 8: 465–470, 1979.
 51. Dockray, G. J., R. A., Gregory, and G. W. Kenner. Immunochemical differences between natural and synthetic big gastrins. Gastroenterology 75: 556, 1978.
 52. Dockray, G. J., R. A., Gregory, H. J. Tracy, and W.‐Y. Zhu. Transport of cholecystokinin‐octapeptide‐like immunoreactivity toward the gut in afferent vagal fibres in cat and dog. J. Physiol. Lond. 314: 501–511, 1981.
 53. Dockray, G. J., R. A., Gregory, H. J. Tracy, and W.‐Y. Zhu. Postsecretory processing of heptadecapeptide gastrin: conversion to C‐terminal immunoreactive fragments in the circulation of the dog. Gastroenterology 83: 224–232, 1982.
 54. Dockray, G. J., and I. L. Taylor. Heptadecapeptide gastrin: measurement in blood by specific radioimmunoassay. Gastroenterology 71: 971–977, 1976.
 55. Dockray, G. J., and H. J. Tracy. Atropine does not abolish cephalic vagal stimulation of gastrin release in dogs. J. Physiol. Lond. 306: 473–480, 1980.
 56. Dockray, G. J., C., Vaillant, and C. R. Hopkins. Biosynthetic relationships of big and little gastrins. Nature Lond. 273: 770–772, 1978.
 57. Dockray, G. J., C., Vaillant, and J. H. Walsh. The neuronal origin of bombesin‐like immunoreactivity in the rat gastrointestinal tract. Neuroscience 4: 1561–1568, 1979.
 58. Dockray, G. J., A. Varro, H. Desmond, J. Young, H. Gregory, and R. A. Gregory. Post‐translational processing of the porcine gastrin precursor by phosphorylation of the COOH‐terminal fragment. J. Biol. Chem. 262: 8643–8647, 1987.
 59. Dockray, G. J., A., Varro, and R. Dimaline. Identification of cholecystokinin in brain: present status. In: Cholecystokinin (CCK) in the Nervous System, edited by J. De Beller‐Oche and G. J. Dockray. Chichester, UK: Horwood, 1984, p. 12–30.
 60. Dockray, G. J., and J. H. Walsh. Amino terminal gastrin fragment in serum of Zollinger‐Ellison syndrome patients. Gastroenterology 68: 222–230, 1975.
 61. Dockray, G. J., J. H., Walsh, and M. I. Grossman. Biological activity of iodinated gastrins. Biochem. Biophys. Res. Commun. 69: 339–345, 1976.
 62. Doyle, J. W., M. M., Wolfe, and J. E. Mcguigan. Hepatic clearance of gastrin and cholecystokinin peptides. Gastroenterology 87: 60–68, 1984.
 63. Dragstedt, L. R., B. C., Walton, and E. R. Woodward. Gastrin, a stimulant of pepsin secretion. Arch. Surg. 86: 304–307, 1963.
 64. Dragstedt, L. R., E. R., Woodward, H. A. Oberhelman, JR., E. H. Storer, and C. A. Smith. Effect of transplantation of antrum of stomach on gastric secretion in experimental animals. Am. J. Physiol. 165: 386–398, 1951.
 65. Dubois, P. M., C., Paulin, and J. A. Chayvialle. Identification of gastrin‐secreting cells and cholecystokinin‐secreting cells in the gastrointestinal tract of the human fetus and adult man. Cell Tissue Res. 175: 351–356, 1976.
 66. Duval, J. W., B., Saffouri, G. G. Weir, J. H. Walsh, A. Arimura, and G. M. Makhlouf. Stimulation of gastrin and somatostatin secretion from the isolated rat stomach by bombesin. Am. J. Physiol. 241 (Gastrointest. Liver Physiol. 4): G242–G247, 1981.
 67. Edkins, J. S. On the chemical mechanism of gastric secretion. Proc. R. Soc. Lond. B Biol. Sci. 76: 376, 1905.
 68. Edkins, J. S. The chemical mechanism of gastric secretion. J. Physiol. Lond. 34: 133–144, 1906.
 69. Edkins, J. S., and M. Tweedy. The natural channels of absorption evoking the chemical mechanism of gastric secretion. J. Physiol. Lond. 38: 263–267, 1909.
 70. Ellison, E. H., and S. D. Wilson. Further observations on factors influencing the symptomatology manifest by patients with Zollinger‐Ellison syndrome. In: Gastric Secretion, edited by T. K. Shnitka, J. A. L. Gilbert, and R. C. Harrison. New York: Pergamon, 1967, p. 363–369.
 71. El Munshid, H. A. G. Liedberg, J. F. Rehfeld, F. Sundler, L.‐I. Larsson, and R. Hakanson. Effect of bilateral nephrectomy on serum gastrin concentration, gastric histamine content, histidine decarboxylase activity, and acid secretion in the rat. Scand. J. Gastroenterol. 11: 87–91, 1976.
 72. Elwin, C. E. Gastric acid responses to antral application of some amino acids, peptides, and isolated fractions of a protein hydrolysate. Scand. J. Gastroenterol. 9: 239–247, 1974.
 73. Euler, A. R., W. J., Byrne, L. M. Cousins, M. E. Ament, R. D. Leake, and J. H. Walsh. Increased serum gastrin concentrations and gastric acid hyposecretion in the immediate newborn period. Gastroenterology 72: 1271–1273, 1977.
 74. Eysselein, V. E., V., Maxwell, T. Reedy, E. Wunsch, and J. H. Walsh. Similar acid stimulatory potencies of synthetic human big and little gastrins in man. J. Clin. Invest. 73: 1284–1290, 1984.
 75. Eysselein, V. E., W., Niebel, and M. V. Singer. Gastrin response to a meal before and after cutting the extrinsic nerves of the stomach in the dog. J. Physiol. Lond. 369: 355–364, 1985.
 76. Farooq, O., and J. H. Walsh. Atropine enhances serum gastrin response to insulin in man. Gastroenterology 68: 662–666, 1975.
 77. Feldman, M., C. T., Richardson, I. L. Taylor, and J. H. Walsh. Effect of atropine on vagal release of gastrin and pancreatic polypeptide. J. Clin. Invest. 63: 294–298, 1979.
 78. Feldman, M., C. T., Richardson, and J. H. Walsh. Sex‐related differences in gastrin release and parietal cell sensitivity to gastrin in healthy human beings. J. Clin. Invest. 71: 715–720, 1983.
 79. Feldman, M., and J. H. Walsh. Acid inhibition of sham feeding‐stimulated gastrin release and gastric acid secretion: effect of atropine. Gastroenterology 78: 772–776, 1980.
 80. Feldman, M., J. H., Walsh, H. C. Wong, and C. T. Richardson. Role of gastrin heptadecapeptide in the acid secretory response to amino acids in man. J. Clin. Invest. 61: 308–313, 1978.
 81. Feng, T. P., H. C., Hou, and R. K. S. Lim. On the mechanism of the inhibition of gastric secretion by fat. Chin. J. Physiol. 3: 371–378, 1929.
 82. Frémont, A. Estomac Isolé Vichy, France: Wallon, 1985, p. 1–31. (Académie de Médecine de Paris. Séance du 14 Mai.)
 83. Fujimoto, S., T., Hattori, K. Kimoto, S. Yamashita, S. Fu‐Jita, and K. Kawai. Tritiated thymidine autoradiographic study on origin and renewal of gastrin cells in antral area of hamsters. Gastroenterology 79: 785–791, 1980.
 84. Gardner, J. D., and R. T. Jensen. Cholecystokinin receptor antagonists. Am. J. Physiol. 246 (Gastrointest. Liver Physiol. 9): G471–G476, 1984.
 85. Gavin, G., E. W., Mchenry, and M. J. Wilson. Histamine in canine gastric tissues. J. Physiol. Lond. 79: 234–238, 1933.
 86. Gillespie, I. E. Inhibition of acid secretion by gastrin extracts. In: Gastrin, edited by M. I. Grossman. London: But‐terworth, 1966, p. 229–254.
 87. Gjuruldsen, S. T., J., Myren, and B. Fietheim. Alternations of gastric mucosa following a graded partial gastrectomy. Scand. J. Gastroenterol. 3: 465–470, 1968.
 88. Gregory, H., P. M., Hardy, D. S. Jones, G. W. Kenner, and R. C. Sheppard. The antral hormone gastrin. I. Structure of gastrin. Nature Lond. 204: 931–933, 1964.
 89. Gregory, R. A. Secretory Mechanisms of the Gastro‐Intestinal Tract London: Arnold, 1962.
 90. Gregory, R. A. Gastric secretion: a review of its chief nervous and hormonal mechanisms. In: Surgical Physiology of the Gastrointestinal Tract, edited by A. N. Smith. Edinburgh: Royal College of Surgeons, 1962, p. 57–70.
 91. Gregory, R. A. Gastrin—the natural history of a peptide hormone. Harvey Led. 64: 121–155, 1970.
 92. Gregory, R. A. The gastrointestinal hormones: a review of recent advances. J. Physiol. Lond. 241: 1–32, 1974.
 93. Gregory, R. A. A review of some recent developments in the chemistry of the gastrins. Bioorg. Chem. 8: 497–511, 1979.
 94. Gregory, R. A. Some aspects of the structure of gastrin and gastrin‐like forms and fragments in gut and brain. In: Gastrins and the Vagus, edited by J. F. Rehfeld and E. Amdrup. London: Academic, 1979, p. 47–55.
 95. Gregory, R. A., G. J., Dockray, J. R. Reeve, JR., J. E. Shively, and C. Miller. Isolation from porcine antral mucosa of a hexapeptide corresponding to the C‐terminal sequence of gastrin. Peptides Fayetteville 4: 319–323, 1983.
 96. Gregory, R. A., and A. C. Ivy. The hormonal stimulation of gastric secretion. Q. J. Exp. Physiol. Cogn. Med. Sci. 31: 112–128, 1942.
 97. Greggory, R. A., and H. J. Tracy. The preparation and properties of gastrin (Abstract). J. Physiol. Lond. 149: 70P, 1959.
 98. Gregory, R. A., and H. J. Tracy. The further purification of gastrin: secretory responses in a human subject (Abstract). J. Physiol. Lond. 154: 52P, 1960.
 99. Gregory, R. A., and H. J. Tracy. The preparation and properties of gastrin. J. Physiol. Lond. 156: 523–543, 1961.
 100. Gregory, R. A., and H. J. Tracy. Constitution and properties of two gastrins extracted from hog antral mucosa (Abstract). J. Physiol. Lond. 169: 18P–19P, 1963.
 101. Gregory, R. A., and H. J. Tracy. The constitution and properties of two gastrins extracted from hog antral mucosa. I. The isolation of two gastrins from hog antral mucosa. II. The properties of two gastrins isolated from hog antral mucosa. Gut 5: 103–117, 1964.
 102. Gregory, R. A., and H. J. Tracy. Isolation of two “big gastrins” from Zollinger‐Ellison tumour tissue. Lancet 2: 797–799, 1972.
 103. Gregory, R. A., and H. J. Tracy. Isolation of two minigastrins from Zollinger‐Ellison tumour tissue. Gut 15: 683–685, 1974.
 104. Gregory, R. A., and H. J. Tracy. The chemistry of the gastrins: some recent advances. In: Gastrointestinal Hormones, edited by J. C. Thompson. Austin: University of Texas Press, 1975, p. 13–24.
 105. Gregory, R. A., and H. J. Tracy. Relative potencies of natural and synthetic human big gastrins. Gastroenterology 87: 1209–1210, 1984.
 106. Gregory, R. A., H. J., Tracy, J. I. Harris, M. J. Runswick, S. Moore, G. W. Kenner, and R. Ramage. Minigastrin: corrected structure and synthesis. Hoppe‐Seyler's Z. Physiol. Chem. 360: 73–85, 1979.
 107. Gross, W. Beitrag zur Kenntnis der Sekretionsbedingungen des magens nach Versuchen am hund. Arch. Verdau‐Kr. 12: 507–516, 1906.
 108. Grossman, M. I. Gastrointestinal hormones. Physiol. Rev. 30: 33–90, 1950.
 109. Grossman, M. I. Hypothesis: gastrin, cholecystokinin and secretin act on one receptor. Lancet 1: 1088–1089, 1970.
 110. Grossman, M. I. Gastrin. 2. Physiology: hormonal effects. In: Investigative and Diagnostic Endocrinology. Peptide Hormones, edited by S. A. Berson and R. S. Yalow. Amsterdam: North‐Holland, 1973, vol. 2B, p. 1034–1037.
 111. Grossman, M. I., and S. J. Konturek. Inhibition of acid secretion in dog by metiamide, a histamine antagonist acting on H2 receptors. Gastroenterology 66: 517–521, 1974.
 112. Grossman, M. I., C. R., Robertson, and A. C. Ivy. Proof of a hormonal mechanism for gastric secretion—the humoral transmission of the distention stimulus. Am. J. Physiol. 153: 1–9, 1948.
 113. Håkanson, R., J., Alumets, M. Ekelund, J. Hedenbro, and F. Sundler. Function and morphology in gastric endocrine cells. In: Cellular Basis of Chemical Messengers in the Digestive System, edited by M. I. Grossman, M. A. B. Brazier, and J. Lechago. New York: Academic, 1981, p. 99–119.
 114. Hakanson, R., J. H., Kroesen, G. Liedberg, J. Oscarson, J. F. Rehfeld, and F. Stadil. Correlation between serum gastrin concentration and rat stomach histidine decarboxylase activity. J. Physiol. Land. 243: 483–498, 1974.
 115. Hille, A., P., Rosa, and W. B. Huttner. Tyrosine sulfation: a posttranslational modification of proteins destined for secretion? FEBS Lett. 177: 129–134, 1984.
 116. Hirschowitz, B. I., R., Gibson, and E. Molina. Atropine suppresses gastrin release by food in intact and vagotomized dogs. Gastroenterology 81: 838–843, 1981.
 117. Hirschowitz, B. I., and G. A. Hutchison. Kinetics of atropine inhibition of pentagastrin‐stimulated H+, electrolyte, and pepsin secretion in the dog. Am. J. Dig. Dis. 22: 99–107, 1977.
 118. Hollinshead, J. W., H. T., Debas, T. Yamada, J. Elashoff, B. Osadchey, and J. H. Walsh. Hypergastrinemia develops within 24 hours of truncal vagotomy in dogs. Gastroenterology 88: 35–40, 1985.
 119. Holst, J. J., S. L., Jensen, S. Knuhtsen, O. V. Nielsen, and J. F. Rehfeld. Effect of vagus, gastric inhibitory polypeptide, and HCl on gastrin and somatostatin release from perfused pig antrum. Am. J. Physiol. 244 (Gastrointest. Liver Physiol. 7): G515–G522, 1983.
 120. Hsu, W. H., and C. W. Cooper. Serum gastrin in the rat: cholinergic and adrenergic effects. Proc. Soc. Exp. Biol. Med. 154: 401–406, 1977.
 121. Huttner, W. B. Sulphation of tyrosine residues—a widespread modification of proteins. Nature Land. 299: 273–276, 1982.
 122. Impicciatore, M., J. H., Walsh, and M. I. Grossman. Low doses of atropine enhance serum gastrin response to food in dogs. Gastroenterology 72: 995–996, 1977.
 123. Isenberg, J. I., J. H., Walsh, E. Passaro, E. W. Moore, and M. I. Grossman. Unusual effect of secretin on serum gastrin, serum calcium and gastric acid secretion in a patient with suspected Zollinger‐Ellison syndrome. Gastroenterology 62: 626–631, 1972.
 124. Ito, R., K., Sato, T. Helmer, G. Jay, and K. Agarwal. Structural analysis of the gene encoding human gastrin: the large intron contains an Alu sequence. Proc. Natl. Acad. Sci. USA 81: 4662–4666, 1984.
 125. Ivy, A. C., and J. I. Farrell. Demonstration of a dog with a transplanted gastric pouch and of a dog with a pancreatic transplant. Am. J. Physiol. 76: 226, 1926. (Proc. Am. Physiol. Soc. Meeting, 38th, Cleveland, Ohio, December 28–30, 1925.)
 126. Ivy, A. C., R. K. S., Lim, and J. E. Mccarthy. Contributions to the physiology of gastric secretion. II. The intestinal phase of gastric secretion. Q. J. Exp. Physiol. 15: 55–68, 1925.
 127. Ivy, A. C., and J. E. Whitlow. The gastrin theory put to physiological test. Am. J. Physiol. 60: 578–588, 1922.
 128. Jensen, D. M., R. W., Mccallum, E. Corazziari, J. Elashoff, and J. H. Walsh. Human lower esophageal sphincter responses to synthetic human gastrins 34 (G34) and 17 (G17). Gastroenterology 79: 431–438, 1980.
 129. Johnson, L. R. Regulation of gastrointestinal growth. In: Physiology of the Gastrointestinal Tract, edited by L. R. Johnson. New York: Raven, 1981, p. 169–196.
 130. Johnson, L. R., D., Aures, and L. Yuen. Pentagastrin‐induced stimulation of protein synthesis in the gastrointestinal tract. Am. J. Physiol. 217: 251–254, 1969.
 131. Jönsson, A.‐C., and G. J. Dockray. Immunohistochemical localization to pyloric antral G cells of peptides derived from porcine preprogastrin. Regul. Pept. 8: 183–290, 1984.
 132. Kato, K., Y., Hayashizaki, Y. Takahashi, S. Himeno, and K. Matsubara. Molecular cloning of the human gastrin gene. Nucleic Acids Res. 11: 8197–8203, 1983.
 133. Kato, K., S., Himeno, Y. Takahashi, T. Wakabayashi, S. Tarui, and K. Matsubara. Molecular cloning of human gastrin precursor cDNA. Gene 26: 53–57, 1983.
 134. Kenner, G. W., S., Moore, K. L. Ramachandran, R. Ramage, G. J. Dockray, R. A. Gregory, L. Hood, and M. Hunkapiller. Porcine big gastrin: sequence, synthesis and immunochemical studies. Bioorg. Chem. 10: 152–160, 1981.
 135. Kenner, G. W., and R. C. Sheppard. Chemical studies of some mammalian gastrins. Proc. R. Soc. Lond. B Biol. Sci. 170: 89–96, 1968.
 136. Knuhtsen, S., J. J., Holst, U. Knigge, M. Olesen, and O. V. Nielsen. Radioimmunoassay, pharmcokinetics and neuronal release of gastrin‐releasing peptide in anesthetized pigs. Gastroenterology 87: 372–378, 1984.
 137. Komarov, S. A. Gastrin. Proc. Soc. Exp. Biol. Med. 38: 514–516, 1938.
 138. Komarov, S. A. Studies on gastrin. I. Methods of isolation of a specific gastric secretagogue from the pyloric mucous membrane and its chemical properties. Rev. Can. Biol. 1: 191–376, 1942.
 139. Komarov, S. A. Studies on gastrin. II. Physiological properties of the specific gastric secretagogue of pyloric mucous membrane. Rev. Can. Biol. 1: 377–392, 1942.
 140. Konturek, S. J., P. L., Rayford, and J. C. Thompson. Effect of pH of gastric and intestinal meals on gastric acid and plasma gastrin and secretin responses in the dog. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E537–E543, 1977.
 141. Konturek, S. J., A., Robert, A. J. Hanchar, and J. E. Nezamis. Comparison of prostacyclin and prostaglandin E2 on gastric secretion, gastrin release, and mucosal blood flow in dogs. Dig. Dis. Sci. 25: 673–679, 1980.
 142. Konturek, S. J., J., Tasler, M. Cieszkowski, D. H. Coy, and A. V. Schally. Effect of growth hormone release‐inhibiting hormone on gastric secretion, mucosal blood flow, and serum gastrin. Gastroenterology 70: 737–741, 1976.
 143. Konturek, S. J., J., Tasler, M. Cieszkowski, M. Dobrzańska, and E. Wünsch. Stimulation of gastrin release and gastric secretion by amino acids bathing pyloric gland area. Am. J. Physiol. 233 (Endocrinol. Metab. Gastrointest. Physiol. 2): E170–E174, 1977.
 144. Koop, H. I., I., Behrens, E. Bothe, H. Koschwitz, C. H. S. Mcintosh, R. A. Pedersen, R. Arnold, and W. Creutzfeldt. Adrenergic control of rat gastric somatostatin and gastrin release. Scand. J. Gastroenterol. 18: 65–71, 1983.
 145. Lamers, C. B., J. H., Walsh, J. B. Jansen, A. R. Harrison, A. F. Ippoliti, and J. H. Van Tongeren. Evidence that gastrin 34 is preferentially released from the human duodenum. Gastroenterology 83: 233–239, 1982.
 146. Larsson, L. I., N., Goltermann, L. Demagistris, J. F. Rehfeld, and T. W. Schwartz. Somatostatin cell processes as pathways for paracrine secretion. Science Wash. DC 205: 1393–1395, 1979.
 147. Larsson, L.‐I., and J. F. Rehfeld. Pituitary gastrins occur in corticotrophs and melanotrophs. Science Wash. DC 213: 768–770, 1981.
 148. Larsson, L.‐I, J. F., Rehfeld, and N. Goltermann. Gastrin in the human fetus: distribution and molecular forms of gastrin in the antropyloric gland area, duodenum and pancreas. Scand. J. Gastroenterol. 12: 869–872, 1977.
 149. Larsson, L.‐I., J. F., Rehfeld, F. Sundler, and R. Håkanson. Pancreatic gastrin in foetal and neonatal rats. Nature Lond. 262: 609–610, 1976.
 150. Lees, F., and L. C. Grandjean. The gastric and jejunal mucosae in healthy patients with partial gastrectomy. Arch. Intern. Med. 101: 943–951, 1958.
 151. Lehy, T., J. P., Accary, D. Labeille, and M. Dubrasquet. Chronic administration of bombesin stimulates antral gastrin cell proliferation in the rat. Gastroenterology 84: 914–919, 1983.
 152. Lehy, T., and G. Willems. Population kinetics of antral gastrin cells in the mouse. Gastroenterology 71: 614–619, 1976.
 153. Lewin, M., A., Soumarmon, J. P. Bali, S. Bonfils, J. P. Girma, J. L. Morgat, and P. Fromageot. Interaction of 3H‐labelled synthetic human gastrin I with rat gastric plasma membranes. Evidence for the existence of biologically reactive gastrin receptor sites. FEBS Lett. 66: 168–172, 1976.
 154. Lichtenberger, L. A search for the origin of neonatal hy‐pergastrinemia. J. Pediatr. Gastroenterol. Nutr. 3: 161–166, 1984.
 155. Lichtenberger, L. M., R., Delansorne, and L. A. Graziani. Importance of amino acid uptake and decarboxylation in gastrin release from isolated G cells. Nature Lond. 295: 698–700, 1982.
 156. Lichtenberger, L. M., L. A., Graziani, and W. P. Dubinsky. Importance of dietary amines in meal‐induced gastrin release. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G341–G347, 1982.
 157. Lichtenberger, L. M., J., Lechago, and L. R. Johnson. Depression of antral and serum gastrin concentration by food deprivation in the rat. Gastroenterology 68: 1473–1479, 1975.
 158. Lim, R. K. S. The question of a gastric hormone. Q. J. Exp. Physiol. 13: 79–103, 1922.
 159. Lim, R. K. S., A. C., Ivy, and J. E. Mccarthy. Contributions to the physiology of gastric secretion. I. Gastric secretion by local (mechanical and chemical) stimulation. Q. J. Exp. Physiol. 15: 13–53, 1925.
 160. Lin, T.‐M., G. L., Southard, and G. F. Spray. Stimulation of gastric acid secretion in the dog by C‐terminal penta‐, tetra‐and tripeptides of gastrin and their O‐methylesters. Gastroenterology 70: 733–736, 1976.
 161. Lucas, A., T. E., Adrian, N. Christofides, S. R. Bloom, and A. Aynsley‐Green. Plasma motilin, gastrin, and enteroglucagon and feeding in the human newborn. Arch. Dis. Child. 55: 673–677, 1980.
 162. Mahachai, V., K., Walker, H. Sevelius, and A. B. R. Thomson. Antisecretory and serum gastrin lowering effect of Enprostil in patients with duodenal ulcer disease. Gastroenterology 89: 555–561, 1985.
 163. Makhlouf, G. M., J. P. A., Mcmanus, and W. I. Card. A comparative study of the effects of gastrin, histamine, histalog and mechothane on the secretory capacity of the human stomach in two normal subjects over 20 months. Gut 6: 525–534, 1965.
 164. Malmstrom, J., F., Stadil, and J. F. Rehfeld. Gastrins in tissue: concentration and component pattern in gastric, duodenal, and jejunal mucosa of normal human subjects and patients with duodenal ulcer. Gastroenterology 70: 697–703, 1976.
 165. Martindale, R., G. L., Kauffman, S. Levin, J. H. Walsh, and T. Yamada. Differential regulation of gastrin and somatostatin secretion from isolated perfused rat stomachs. Gastroenterology 83: 240–244, 1982.
 166. Martinez, J., J.‐P., Bali, R. Magous, J. Laur, M.‐F. Lignon, C. Briet, D. Nisato, and B. Castro. Structure‐activity relationships of C‐terminal tri‐ and tetrapeptide fragments that inhibit gastrin activity. J. Med. Chem. 28: 273–278, 1985.
 167. Martinez, J., R., Magous, M.‐F. Lignon, J. Laur, B. Castro, and J.‐P. Bali. Synthesis and biological activity of new peptide segments of gastrin exhibiting gastrin antagonist property. J. Med. Chem. 27: 1597–1601, 1984.
 168. Mcdonald, T. J., H., Jörnvall, G. Nilsson, M. Vagne, M. Ghatei, S. R. Bloom, and V. Mutt. Characterization of a gastrin releasing peptide from porcine non‐antral gastric tissue. Biochem. Biophys. Res. Commun. 90: 227–233, 1979.
 169. Mcdonald, T. J., G., Nilsson, M. Vagne, M. Ghatei, S. R. Bloom, and V. Mutt. A gastrin releasing peptide from the porcine non‐antral gastric tissue. Gut 19: 767–774, 1978.
 170. Mcguigan, J. E. Immunochemical studies with synthetic human gastrin. Gastroenterology 54: 1005–1011, 1968.
 171. Mcguigan, J. E. Gastric mucosal intracellular localization of gastrin by immunofluorescence. Gastroenterology 55: 315–327, 1968.
 172. Mcintosh, C., V., Bakich, T. Trotter, Y. N. Kwok, E. Nishimura, R. Pederson, and J. Brown. Effect of cysteamine on secretion of gastrin and somatostatin from the rat stomach. Gastroenterology 86: 834–838, 1984.
 173. Melrose, A. G., R. I., Russell, and A. Dick. Gastric mucosal structure and function after vagotomy. Gut 5: 546–549, 1964.
 174. Morley, J. S. Structure‐function relationships in gastrin‐like peptides. Proc. R. Soc. Lond. B Biol. Sci. 170: 97–111, 1968.
 175. Morley, J. S., H. J., Tracy, and R. A. Gregory. Structure‐function relationships in the active C‐terminal tetrapeptide sequence of gastrin. Nature Lond. 207: 1356–1359, 1965.
 176. Nahrwold, D. L., A. R., Cooke, and M. I. Grossman. Choleresis induced by stimulation of gastric antrum. Gastroenterology 52: 18–22, 1967.
 177. Nilsson, G., J., Simon, R. S. Yalow, and S. A. Berson. Plasma gastrin and gastric acid responses to sham feeding and feeding in dogs. Gastroenterology 63: 51–59, 1972.
 178. Nilsson, G., R. S., Yalow, and S. A. Berson. Distribution of gastrin in the gastrointestinal tract of human, dog, cat and hog. In: Frontiers in Gastrointestinal Hormone Research, edited by S. Andersson. Stockholm: Almqvist & Wiksell, 1972, p. 95–101.
 179. Noyes, B. E., M., Mevarech, R. Stein, and K. L. Agarwal. Detection and partial sequence analysis of gastrin mRNA by using an oligodeoxynucleotide probe. Proc. Natl. Acad. Sci. USA 76: 1770–1774, 1979.
 180. Oberhelman, H. A., JR., E. R. Woodward, J. M. Zubiran, and L. R. Dragstedt. Physiology of the gastric antrum. Am. J. Physiol. 169: 738–748, 1952.
 181. Pauwels, S., H. P., Desmond, R. Dimaline, and G. J. Dockray. Identification of progastrin in gastrinomas, antrum and duodenum by novel radioimmunoassay. J. Clin. Invest. 77: 376–381, 1986.
 182. Pauwels, S., and G. J. Dockray. Identification of NH2‐terminal fragments of big gastrin in plasma. Gastroenterology 82: 56–61, 1982.
 183. Pauwels, S., G. J. Dockray, and R. Walker. Comparison of the metabolism of sulfated and unsulfated heptadecapeptide gastrin in humans. Gastroenterology 92: 1220–1225, 1987.
 184. Pauwels, S., G. J., Dockray, R. Walker, and S. Marcus. N‐terminal tryptic fragment of big gastrin: metabolism and failure to influence gastrin 17‐evoked acid secretion in humans. Gastroenterology 86: 86–92, 1984.
 185. Pauwels, S., G. J., Dockray, R. Walker, and S. Marcus. Metabolism of heptadecapeptide gastrin in humans studied by region‐specific antisera. J. Clin. Invest. 75: 2006–2013, 1985.
 186. Pauwels, S., G. J., Dockray, R. Walker, and S. Marcus. Metabolism of the 1–13 sequence of gastrin 17 in humans and failure to influence acid secretion. Gastroenterology 89: 49–56, 1985.
 187. Peters, M. N., M., Feldman, J. H. Walsh, and C. T. Richardson. Effect of gastric alkalinization on serum gastrin concentrations in humans. Gastroenterology 85: 35–39, 1983.
 188. Peters, M. N., J. H., Walsh, J. Ferrari, and M. Feldman. Adrenergic regulation of distention‐induced gastrin release in humans. Gastroenterology 82: 659–663, 1982.
 189. Petersen, B., J., Christiansen, and J. F. Rehfeld. The N‐terminal tridecapeptide fragment of gastrin‐17 inhibits gastric acid secretion. Regul. Pept. 7: 323–334, 1983.
 190. Peterson, W., M., Feldman, I. Taylor, and M. Bremer. The effect of 15 (R)‐15‐methyl prostaglandin E2 on meal‐stimulated gastric acid secretion, serum gastrin, and pancreatic polypeptide in duodenal ulcer patients. Dig. Dis. Sci. 24: 381–384, 1979.
 191. Popielski, L. Über die physiologische wirkung von extracten aus sämtlichen Teilen des verdaungskanales (Magen, Dick‐und Dünndarm) sowie des Gehirns, Pankreas und Blutes und über die chemischen Eigenschaften des darin wirkenden Körpers. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 128: 191–221, 1909.
 192. Popielski, L. β‐Imidazolyläthylamin und die Organextrakte I. β‐imidazolyäthylamin als mächtiger erreger der Magendrüsen. Pfluegers Arch. Gesamte Physiol. Menschen Tiere 178: 214–259, 1919.
 193. Power, D. M., N., Bunnett, and R. Dimaline. Chromatographic and immunochemical studies on postsecretory processing of gastrin in the pig. Am. J. Physiol. 251 (Gastrointest. Liver Physiol. 14): G300–G307, 1986.
 194. Power, D. M., N., Bunnett, A. J. Turner, and R. Dimaline. Degradation of endogenous heptadecapeptide gastrin by endopeptidase 24.11 in the pig. Am. J. Physiol. 253 (Gastrointest. Liver Physiol. 16): G33–G39, 1987.
 195. Preshaw, R. M., A. R., Cooke, and M. I. Grossman. Pancreatic secretion induced by stimulation of the pyloric gland area of the stomach. Science Wash. DC 148: 1347–1348, 1965.
 196. Rahier, J., S. Pauwels, and G. J. Dockray. Biosynthesis of gastrin: localization of the precursor and peptide products using electron microscopic‐immunogold methods. Gastroenterology 92: 1146–1152, 1987.
 197. Reeve, J. R., JR., R. Dimaline, J. E. Shively, D. Hawke, P. Chew, and J. H. Walsh. Unique amino‐terminal structure of rat little gastrin. Peptides Fayetteville 2: 453–458, 1981.
 198. Reeve, J. R., JR., J. H. Walsh, R. K. Tompkins, D. Hawke, and J. E. Shively. Amino terminal fragments of human progastrin from gastrinoma. Biochem. Biophys. Res. Commun. 123: 404–409, 1984.
 199. Rehfeld, J. F. Localisation of gastrins to neuro‐ and ade‐nohypophysis. Nature Lond. 271: 771–773, 1978.
 200. Rehfeld, J. F. Tetrin, In: Gut Hormones (2nd ed.), edited by S. R. Bloom and J. M. Polack. Edinburgh: Churchill‐Livingstone, 1981, p. 240–247.
 201. Rehfeld, J. F., H. F., Hansen, L.‐I. Larsson, K. Stengaard‐Pedersen, and N. A. Thorn. Gastrin and cholecystokinin in pituitary neurons. Proc. Natl. Acad. Sci. USA 81: 1902–1905, 1984.
 202. Rehfeld, J. F., and L.‐I. Larsson. The predominating molecular form of gastrin and cholecystokinin in the gut is a small peptide corresponding to their COOH‐terminal tetra‐peptide amide. Acta Physiol. Scand. 105: 117–119, 1979.
 203. Rehfeld, J. F., and L.‐I. Larsson. Pituitary gastrins: different processing in corticotrophs and melanotrophs. J. Biol. Chem. 256: 10426–10429, 1981.
 204. Rehfeld, J. F., L.‐I., Larsson, N. R. Goltermann, T. W. Schwartz, J. J. Holst, S. L. Jensen, and J. S. Morley. Neural regulation of pancreatic hormone secretion by the C‐terminal tetrapeptide of CCK. Nature Lond. 284: 33–38, 1980.
 205. Rehfeld, J. F., and J. M. Lundberg. Cholecystokinin in feline vagal and sciatic nerves: concentration, molecular form and transport velocity. Brain Res. 275: 341–347, 1983.
 206. Rehfeld, J. F., T. W., Schwartz, and F. Stadil. Immunochemical studies on macromolecular gastrins: evidence that “big big gastrins” are artifacts in blood and mucosa, but truly present in some large gastrinomas. Gastroenterology 73: 469–477, 1977.
 207. Rehfeld, J. F., and F. Stadil. Gel filtration studies on immunoreactive gastrin in serum from Zollinger‐Ellison patients. Gut 14: 369–373, 1973.
 208. Richardson, C. T., J. H., Walsh, M. I. Hicks, and J. S. Fordtran. Studies on the mechanisms of food‐stimulated gastric acid secretion in normal human subjects. J. Clin. Invest. 58: 623–631, 1976.
 209. Rosenquist, G. L., and J. H. Walsh. Radioimmunoassay of gastrin. In: Gastrointestinal Hormones, edited by G. B. Glass. New York: Raven, 1980, p. 769–795.
 210. Ryan, G. P., E. M., Copeland, and L. R. Johnson. Effects of gastrin and vagal denervation on DNA synthesis in canine fundic mucosa. Am. J. Physiol. 235 (Endocrinol. Metab. Gastrointest. Physiol. 4): E32–E36, 1978.
 211. Sacks, J., A. C., Ivy, J. P. Burgess, and J. E. Vandolah. Histamine as the hormone for gastric secretion. Am. J. Physiol. 101: 331–338, 1932.
 212. Saffouri, B., J. W., Duval, A. Arimura, and G. M. Makhlouf. Effects of vasoactive intestinal peptide and secretin on gastrin and somatostatin secretion in the perfused rat stomach. Gastroenterology 86: 839–842, 1984.
 213. Saffouri, B., J. W., Duval, and G. M. Makhlouf. Stimulation of gastrin secretion in vitro by intraluminal chemicals; regulation by intramural cholinergic and noncholinergic neurons. Gastroenterology 87: 557–561, 1984.
 214. Saffouri, B., G., Weir, K. Bitar, and G. Maklhouf. Stimulation of gastrin secretion from the perfused rat stomach by somatostatin antiserum. Life Sci. 25: 1749–1754, 1979.
 215. Saffouri, B., G. C., Weir, K. N. Bitar, and G. M. Makhlouf. Gastrin and somatostatin secretion by perfused rat stomach: functional linkage of antral peptides. Am. J. Physiol. 238 (Gastrointest. Liver Physiol. 1): G495–G501, 1980.
 216. Schiller, L. R., J. H., Walsh, and M. Feldman. Distention‐induced gastrin release: effects of luminal acidification and intravenous atropine. Gastroenterology 78: 912–917, 1980.
 217. Schiller, L. R., J. H., Walsh, and M. Feldman. Effect of atropine on gastrin release stimulated by an amino acid meal in humans. Gastroenterology 83: 267–272, 1982.
 218. Schrumpf, E., L. S., Semb, and H. Vold. Metabolic clearance and disappearance rates of synthetic human gastrin in man. Scand. J. Gastroenterol. 8: 731–734, 1973.
 219. Schubert, M. L., K. N., Bitar, and G. M. Makhlouf. Regulation of gastrin and somatostatin secretion by cholinergic and noncholinergic intramural neurons. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G442–G447, 1982.
 220. Schubert, M. L., and G. M. Makhlouf. Regulation of gastrin and somatostatin secretion by intramural neurons: effect of nicotinic receptor stimulation with dimethyl‐phenylpiperazinium. Gastroenterology 83: 626–632, 1982.
 221. Schubert, M. L., B., Saffouri, J. H. Walsh, and G. M. Makhlouf. Inhibition of neurally mediated gastrin secretion by bombesin antiserum. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G456–462, 1985.
 222. Schusdziarra, V., V., Harris, J. M. Conlon, A. Arimura, and R. Unger. Pancreatic and gastric somatostatin release in response to intragastric and intraduodenal nutrients and HCl in the dog. J. Clin. Invest. 62: 509–518, 1978.
 223. Seal, A., T., Yamada, H. Debas, J. Hollinshead, B. Osad‐Chey, G. Aponte, and J. Walsh. Somatostatin‐14 and ‐28: clearance and potency on gastric function in dogs. Am. J. Physiol. 243 (Gastrointest. Liver Physiol. 6): G97–G102, 1982.
 224. Short, G. M., J. W., Doyle, and M. M. Wolfe. Effect of antibodies to somatostatin on acid secretion and gastrin release by the isolated perfused rat stomach. Gastroenterology 88: 984–988, 1985.
 225. Short, G. M., G. M., Reel, J. W. Doyle, and M. M. Wolfe. Effect of GRP on β‐adrenergic‐stimulated gastrin and somatostatin release in the isolated rat stomach. Am. J. Physiol. 249 (Gastrointest. Liver Physiol. 12): G197–G202, 1985.
 226. Shulkes, A., P., Chick, and K. J. Hardy. Fetal and maternal production and metabolism of gastrin in sheep. J. Endocrinol. 94: 183–189, 1982.
 227. Soares, E. C., S., Zaterka, and J. H. Walsh. Acid secretion and serum gastrin at graded intragastric pressures in man. Gastroenterology 72: 676–679, 1977.
 228. Solcia, E., G., Vassallo, and R. Sampietro. Endocrine cells in the antro‐pyloric mucosa of the stomach. Z. Zellforsch. 81: 474–486, 1967.
 229. Soll, A. H. The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells. J. Clin. Invest. 61: 370–380, 1978.
 230. Soll, A. H. The interaction of histamine with gastrin and carbamylcholine on oxygen uptake by isolated mammalian parietal cells. J. Clin. Invest. 61: 381–389, 1978.
 231. Soll, A. H. Secretagogue stimulation of [14C]aminopyrine accumulation by isolated canine parietal cells. Am. J. Physiol. 238 (Gastrointest. Liver Physiol. 1): G366–G375, 1980.
 232. Soll, A. H., D. A., Amirian, J. Park, J. D. Elashoff, and T. Yamada. Cholecystokinin potently releases somatostatin from canine fundic mucosal cells in short‐term culture. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G569–G573, 1985.
 233. Soll, A. H., D. A., Amirian, L. P. Thomas, J. Park, J. D. Elashoff, M. A. Beaven, and T. Yamada. Gastrin receptors on nonparietal cells isolated from canine fundic mucosa. Am. J. Physiol. 247 (Gastrointest. Liver Physiol. 10): G715–G723, 1984.
 234. Soll, A. H., D. A., Amirian, L. P. Thomas, T. J. Reedy, and J. D. Elashoff. Gastrin receptors on isolated canine parietal cells. J. Clin. Invest. 73: 1434–1447, 1984.
 235. Stadil, F. Effect of vagotomy on gastrin release during insulin hypoglycaemia in ulcer patients. Scand. J. Gastroenterol. 7: 225–231, 1972.
 236. Steiner, D. F. Proinsulin. Triangle Engl. Ed. 11: 51–60, 1972.
 237. Stern, D. H., and J. H. Walsh. Gastrin release in postoperative ulcer patients: evidence for release of duodenal gastrin. Gastroenterology 64: 363–369, 1973.
 238. Strunz, U. T., C. F., Code, and M. I. Grossman. Effect of gastrin on electrical activity of antrum and duodenum of dogs. Proc. Soc. Exp. Biol. Med. 161: 25–27, 1979.
 239. Strunz, U. T., M. R., Thompson, J. Elashoff, and M. I. Grossman. Hepatic inactivation of gastrins of various chain lengths in dogs. Gastroenterology 74: 550–553, 1978.
 240. Strunz, U. T., J. H., Walsh, and M. I. Grossman. Removal of gastrin by various organs in dogs. Gastroenterology 74: 32–33, 1978.
 241. Strunz, U. T., J. H., Walsh, and M. I. Grossman. Stimulation of gastrin release in dogs by individual amino acids. Proc. Soc. Exp. Biol. Med. 157: 440–441, 1978.
 242. Sue, R., M. L., Toomey, A. Todisco, A. H. Soll, and T. Yamada. Pirenzepine‐sensitive muscarinic receptors regulate gastric somatostatin and gastrin. Am. J. Physiol. 248 (Gastrointest. Liver Physiol. 11): G184–G187, 1985.
 243. Sugano, K., G. W., Aponte, and T. Yamada. Identification and characterization of glycine‐extended post‐translational processing intermediates of progastrin in porcine stomach. J. Biol. Chem. 260: 11724–11729, 1985.
 244. Sugano, K., and T. Yamada. Progastrin‐like immunoreactivity in porcine antrum: identification and characterization with region‐specific antisera. Biochem. Biophys. Res. Commun. 126: 72–77, 1985.
 245. Takeuchi, K., W., Peitsch, and L. R. Johnson. Mucosal gastrin receptor. V. Development in newborn rats. Am. J. Physiol. 240 (Gastrointest. Liver Physiol. 3): G163–G169, 1981.
 246. Takeuchi, K., G. R., Speir, and L. R. Johnson. Mucosal gastrin receptor. I. Assay standardization and fulfillment of receptor criteria. Am. J. Physiol. 237 (Endocrinol. Metab. Gastrointest. Physiol. 6): E284–E294, 1979.
 247. Takeuchi, K., G. R., Speir, and L. R. Johnson. Mucosal gastrin receptor. III. Regulation by gastrin. Am. J. Physiol. 238 (Gastrointest. Liver Physiol. 1): G135–G140, 1980.
 248. Tallan, H. H., S. T., Bella, W. H. Stein, and S. Moore. Tyrosine‐O‐sulfate as a constituent of normal human urine. J. Biol. Chem. 217: 703–708, 1955.
 249. Taylor, I. L., W. J., Byrne, D. L. Christie, M. E. Ament, and J. H. Walsh. Effect of individual L‐amino acids on gastric acid secretion and serum gastrin and pancreatic polypeptide release in humans. Gastroenterology 83: 273–278, 1982.
 250. Taylor, I. L., R. A., Sells, R. B. Mcconnell, and G. J. Dockray. Serum gastrin in patients with chronic renal failure. Gut 21: 1062–1067, 1980.
 251. Taylor, I. L., J. H., Walsh, D. Carter, J. Wood, and M. I. Grossman. Effects of atropine and bethanechol on bombesin‐stimulated release of pancreatic polypeptide and gastrin in dog. Gastroenterology 77: 714–718, 1979.
 252. Temperley, J. M., B. H., Stagg, and J. H. Wyllie. Disappearance of gastrin and pentagastrin in the portal circulation. Gut 12: 372–376, 1971.
 253. Tepperman, B. L., J. H., Walsh, and R. M. Preshaw. Effect of antral denervation on gastrin release by sham feeding and insulin hypoglycemia in dogs. Gastroenterology 63: 973–980, 1972.
 254. Track, N. S., C., Creutzfeldt, J. Litzenberger, C. Neuhoff, R. Arnold, and W. Creutzfeld. Appearance of gastrin and somatostatin in the human fetal stomach, duodenum and pancreas. Digestion 19: 292–306, 1979.
 255. Tracy, H. J., and R. A. Gregory. Physiological properties of a series of synthetic peptides structurally related to gastrin I. Nature Land. 204: 935–938, 1964.
 256. 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.
 257. Uvnäs, B. The part played by the pyloric region in the cephalic phase of gastric secretion. Acta Physiol. Scand. 4, Suppl. 13: 1–86, 1942.
 258. Uvnäs, B., K., Uvnäs‐Wallensten, and G. Nilsson. Release of gastrin on vagal stimulation in the cat. Acta. Physiol. Scand. 94: 167–176, 1975.
 259. Uvnäs‐Wallensten, K., and J. F. Rehfeld. Molecular forms of gastrin in antral mucosa, plasma and gastric juice during vagal stimulation of anesthetized cats. Acta. Physiol. Scand. 98: 217–226, 1976.
 260. Uvnäs‐Wallensten, K., J. F., Rehfeld, L.‐I. Larsson, and B. Uvnäs. Heptadecapeptide gastrin in the vagal nerve. Proc. Natl. Acad. Sci. USA 74: 5707–5710, 1977.
 261. Uy, R., and F. Wold. Post‐translational covalent modification of proteins. Science Wash. DC 198: 890–896, 1977.
 262. Vaillant, C., G. J., Dockray, and C. R. Hopkins. Cellular origins of different forms of gastrin. The specific immuno‐cytochemical localization of related peptides. J. Histochem. Cytochem. 27: 932–935, 1979.
 263. Valenzuela, J. E., J. H., Walsh, and J. I. Isenberg. Effect of gastrin on pancreatic enzyme secretion and gallbladder emptying in man. Gastroenterology 71: 409–411, 1976.
 264. Vanderhaeghen, J. J., J. C., Signeau, and W. Gepts. New peptide in the vertebrate CNS reacting with antigastrin antibodies. Nature Lond. 257: 604–605, 1975.
 265. Varndell, I. M., A., Harris, F. J. Tapia, N. Yanaihara, J. Demey, S. R. Bloom, and J. M. Polak. Intracellular topography of immunoreactive gastrin demonstrated using electron immunocytochemistry. Experientia Basel 39: 713–717, 1983.
 266. Varro, V., L., Varga, L. Csernay, J. Nafradi, B. Penke, and L. Balaspiri. Hepatic and mesenteric metabolism of C‐terminal pentapeptide of gastrin in the rat. Acta Hepato‐Gastroenterol. 20: 507–512, 1973.
 267. Walsh, J. H., H. T., Debas, and M. I. Grossman. Pure human big gastrin: immunochemical properties, disappearance half time, and acid‐stimulating action in dogs. J. Clin. Invest. 54: 477–485, 1974.
 268. Walsh, J. H., and M. I. Grossman. Gastrin. N. Engl. J. Med. 292: 1324–1332, 1377–1384, 1975.
 269. Walsh, J. H., J. I., Isenberg, J. Ansfield, and V. Maxwell. Clearance and acid‐stimulating action of human big and little gastrins in duodenal ulcer subjects. J. Clin. Invest. 57: 1125–1131, 1976.
 270. Walsh, J. H., and L. Laster. Enzymatic deamidation of the C‐terminal tetrapeptide amide of gastrin by mammalian tissues. Biochem. Med. 8: 432–439, 1973.
 271. Walsh, J. H., C. T., Richardson, and J. S. Fordtran. pH dependence of acid secretion and gastrin release in normal and ulcer subjects. J. Clin. Invest. 55: 462–467, 1975.
 272. Walsh, J. H., R. S., Yalow, and S. A. Berson. The effect of atropine on plasma gastrin response to feeding. Gastroenterology 60: 16–21, 1971.
 273. Wiborg, O., L., Berglund, E. Boel, F. Norris, K. Norris, J. F. Rehpeld, K. A. Marcker, and J. Vuust. Structure of a human gastrin gene. Proc. Natl. Acad. Sci. USA 81: 1067–1069, 1984.
 274. Woodward, E. R., R. R., Bigelow, and L. R. Dragstedt. Effect of resection of antrum of stomach on gastric secretion in Pavlov pouch dogs. Am. J. Physiol. 162: 99–109, 1950.
 275. Wunsch, E., G., Wendlberger, L. Mladenova‐Orlinova, W. Göhring, E. Jaeger, R. Scharf, R. A. Gregory, and G. J. Dockray. Totalsynthese des Human‐Big‐Gastrins. I. Revidierte Primärstruktur. Hoppe‐Seyler's Z. Physiol. Chem. 362: 179–183, 1981.
 276. Yalow, R. S., and S. A. Berson. Size and charge distinctions between endogenous human plasma gastrin in peripheral blood and heptadecapeptide gastrins. Gastroenterology 58: 609–615, 1970.
 277. Yalow, R. S., and S. A. Berson. Further studies on the nature of immunoreactive gastrin in human plasma. Gastroenterology 60: 203–214, 1971.
 278. Yalow, R. S., and S. A. Berson. And now, “big big” gastrin. Biochem. Biophys. Res. Commun. 48: 391–395, 1972.
 279. Yalow, R. S., and N. Wu. Additional studies on the nature of big big gastrin. Gastroenterology 65: 19–27, 1973.
 280. Yoo, O. J., C. T., Powell, and K. L. Agarwal. Molecular cloning and nucleotide sequence of full‐length cDNA coding for porcine gastrin. Proc. Natl. Acad. Sci. USA 79: 1049–1053, 1982.
 281. Zelenkova, J., and O. Gregor. Development of gastrin activity. Scand J. Gastroenterol. 6: 653–656, 1971.

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

Article Title: Gastrin
 

How to Cite

G. J. Dockray, R. A. Gregory. Gastrin. Compr Physiol 2011, Supplement 17: Handbook of Physiology, The Gastrointestinal System, Neural and Endocrine Biology: 311-336. First published in print 1989. doi: 10.1002/cphy.cp060215