Comprehensive Physiology Wiley Online Library

Cellular Regulation of Amylase Secretion by the Parotid Gland

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Abstract

The sections in this article are:

1 Composition of Rat Parotid Saliva
2 Ultrastructure of Rat Parotid Gland
3 Neurotransmitter Receptors
4 Parotid Slice System
5 Cyclic Adenosine 5'‐Monophosphate
5.1 Evidence for Involvement in Amylase Release
5.2 Mechanism of Action
6 Calcium
6.1 Evidence for Involvement in Amylase Release
6.2 Source of Calcium Mobilized by β‐Adrenergic Agonists
6.3 Mechanism of Calcium Mobilization
6.4 Mechanism of Action
7 Endogenous Protein Phosphorylation
8 Speculations
Figure 1. Figure 1.

Effect of carbachol on phosphorylation of endogenous parotid phosphoproteins. Autoradiograms of selected sucrose gradient fractions from carbachol‐stimulated (+) and nonstimulated (‐) rat parotid gland slices; carbachol concentration = 10 μM. Arrowheads indicate (from top) 18‐kDa and 16‐kDa proteins whose phosphorylation is decreased by carbachol (.3 M sucrose tracks), 31‐kDa protein whose phosphorylation is increased by carbachol (.8 M sucrose), 22.5‐kDa and 20.5‐kDa proteins whose phosphorylation is unaffected by carbachol 1.2 M sucrose), and 24‐kDa protein whose phosphorylation is decreased by carbachol 1.7 M sucrose). (See ref. 128 for experimental details.)

Figure 2. Figure 2.

Diagram of working hypothesis of mechanism of β‐agonist‐induced amylase secretion from rat parotid gland. A: norepinephrine (NE) binds to β‐receptor, activating adenylate cyclase (AC), resulting in increased production of cAMP that dissociates cAMP‐dependent protein kinase (R2C2), liberating free catalytic subunit (C). B: catalytic subunit (C) phosphorylates 92.5‐kDa protein associated with secretory granule (SG) membrane and 20.5‐kDa and 22.5‐kDa proteins associated with endoplasmic reticulum (ER). Phosphorylation of one or both ER‐associated proteins results in release of Ca2+ from cisterna of ER to cytoplasm by unknown mechanism. C: mobilized Ca2+ activates a phosphoprotein phosphatase that dephosphorylates 16‐kDa and 18‐kDa cytoplasmic proteins (function unknown) and 24‐kDa protein associated with SG membrane. D: as a result of phosphorylation of 92.5‐kDa SG membrane‐associated protein and dephosphorylation of 24‐kDaSG membrane‐associated protein, SG fuses to plasma membrane (PM) and ruptures at point of contact, releasing contents into ductal lumen.



Figure 1.

Effect of carbachol on phosphorylation of endogenous parotid phosphoproteins. Autoradiograms of selected sucrose gradient fractions from carbachol‐stimulated (+) and nonstimulated (‐) rat parotid gland slices; carbachol concentration = 10 μM. Arrowheads indicate (from top) 18‐kDa and 16‐kDa proteins whose phosphorylation is decreased by carbachol (.3 M sucrose tracks), 31‐kDa protein whose phosphorylation is increased by carbachol (.8 M sucrose), 22.5‐kDa and 20.5‐kDa proteins whose phosphorylation is unaffected by carbachol 1.2 M sucrose), and 24‐kDa protein whose phosphorylation is decreased by carbachol 1.7 M sucrose). (See ref. 128 for experimental details.)



Figure 2.

Diagram of working hypothesis of mechanism of β‐agonist‐induced amylase secretion from rat parotid gland. A: norepinephrine (NE) binds to β‐receptor, activating adenylate cyclase (AC), resulting in increased production of cAMP that dissociates cAMP‐dependent protein kinase (R2C2), liberating free catalytic subunit (C). B: catalytic subunit (C) phosphorylates 92.5‐kDa protein associated with secretory granule (SG) membrane and 20.5‐kDa and 22.5‐kDa proteins associated with endoplasmic reticulum (ER). Phosphorylation of one or both ER‐associated proteins results in release of Ca2+ from cisterna of ER to cytoplasm by unknown mechanism. C: mobilized Ca2+ activates a phosphoprotein phosphatase that dephosphorylates 16‐kDa and 18‐kDa cytoplasmic proteins (function unknown) and 24‐kDa protein associated with SG membrane. D: as a result of phosphorylation of 92.5‐kDa SG membrane‐associated protein and dephosphorylation of 24‐kDaSG membrane‐associated protein, SG fuses to plasma membrane (PM) and ruptures at point of contact, releasing contents into ductal lumen.

References
 1. Abe, K., and C. Dawes. Dopamine‐induced secretion of protein and of some electrolytes by rat submandibular and parotid glands. Arch. Oral. Biol. 27: 635–643, 1982.
 2. Afari, G., A. Tenenhouse, and J. Klein. The effect of ouabain and of Ca2+ deprivation on isoproterenol‐ and DBcAMP‐stimulated protein secretion from the superfused rat parotid gland. Can. J. Physiol. Pharmacol. 55: 419–426, 1977.
 3. Afari, G., A. Tenenhouse, and C. Vachon. The effects of theophylline and 4‐‐butoxy‐4‐methoxybenzyl)‐2‐imidazolidinone (RO 20–1724) on protein secretion from rat parotid gland. Br. J Pharmacol. 77: 405–411, 1982. Akerman, K. E. O., and D. G. Nicholls. Physiological and bioenergetic aspects of mitochondrial calcium transport. Rev. Physiol. Biochem. Pharmacol. 95: 149–201, 1983.
 4. Amsterdam, A., I. Ohad, and M. Schramm. Dynamic changes in the ultrastructure of the acinar cell of the rat parotid gland during the secretory cycle. J. Cell Biol. 41: 753–773, 1969.
 5. Argent, B. E., and S. Arkle. Mechanism of action of extracellular calcium on isoprenaline‐evoked amylase secretion from isolated rat parotid glands. J. Physiol. Lond. 369: 337–353, 1985.
 6. Argent, B. E., S. Arkle, P. D. Pickford, and P. S. Schofield. The effects of trifluoperazine on amylase secretion by the in vitro rat parotid gland (Abstract). J. Physiol. Lond. 354: 38P, 1984.
 7. Au, D. K., C. C. Malbon, and F. R. Butcher. Identification and characterization of beta‐adrenergic receptors in rat parotid membranes. Biochim. Biophys. Acta 500: 361–371, 1977.
 8. Badad, H., R. Ben‐Zvi, A. Bdolah, and M. Schramm. The mechanism of enzyme secretion by the cell. 4. Effects of inducers, substrates and inhibitors on amylase secretion by rat parotid slices. Eur. J. Biochem. 1: 96–101, 1967.
 9. Batzri, S., and Z. Selinger. Enzyme secretion mediated by the epinephrine β‐receptor in rat parotid slices. Factors governing efficiency of the process. J. Biol. Chem. 248: 356–360, 1973.
 10. Batzri, S., Z. Selinger, and M. Schramm. Potassium ion release and enzyme secretion: adrenergic regulation by α‐ and β‐receptors. Science Wash. DC 174: 1029–1031, 1971.
 11. Batzri, S., Z. Selinger, M. Schramm, and M. R. Robinovitch. Potassium release mediated by the epinephrine α‐receptor in rat parotid slices. Properties and relation to enzyme secretion. J. Biol. Chem. 248: 361–368, 1973.
 12. Baum, B. J., F. T. Colpo, and C. R. Filburn. Characterization and relationship to exocrine secretion of rat parotid gland cyclic AMP‐dependent protein kinase. Arch. Oral Biol. 26: 333–337, 1981.
 13. Baum, B. J., J. M. Freiberg, H. Ito, G. S. Roth, and C. R. Filburn. β‐Adrenergic regulation of protein phosphorylation and its relationship to exocrine secretion in dispersed rat parotid gland acinar cells. J. Biol. Chem. 256: 9731–9736, 1981.
 14. Bdolah, A., R. Ben‐Zvi, and M. Schramm. The mechanism of enzyme secretion by the cell. II. Secretion of amylase and other proteins by slices of rat parotid gland. Arch. Biochem. Biophys. 104: 58–66, 1964.
 15. Bdolah, A., and M. Schramm. Factors controlling the process of enzyme secretion by the rat parotid slice. Biochem. Biophys. Res. Commun. 8: 266–270, 1962.
 16. Bdolah, A., and M. Schramm. The function of 3'5' cyclic AMP in enzyme secretion. Biochem. Biophys. Res. Commun. 18: 452–454, 1965.
 17. Berridge, M. J., and R. F. Irvine. Inositol trisphosphate, a novel second messenger in cellular signal transduction. Nature Lond. 312: 315–321, 1984.
 18. Bodner, L., M. T. Hoopes, M. Gee, H. Ito, G. S. Roth, and B. J. Baum. Multiple transduction mechanisms are likely involved in calcium‐mediated exocrine secretory events in rat parotid cells. J. Biol. Chem. 258: 2774–2777, 1983.
 19. Bonis, D., and B. Rossignol. Effect of sodium and potassium on ATP‐dependent Ca2+ uptake in rat parotid microsomes. FEBS Lett. 137: 63–66, 1982.
 20. Borle, A. B. Cyclic AMP stimulation of calcium efflux from kidney, liver, and heart mitochondria. J. Membr. Biol. 16: 221–236, 1974.
 21. Borle, A. B. Cyclic AMP stimulation of calcium efflux from mitochondria: a negative report. J. Membr. Biol. 29: 209–210, 1976.
 22. Brodin, E., R. Ekman, J. Ekstrom, R. Hakanson, and F. Sundler. Effect of denervation on substance P and vasoactive intestinal peptide in rat salivary glands (Abstract). J. Physiol. Lond. 348: 67P, 1983.
 23. Brodin, E., and G. Nilsson. Concentration of substance P‐like immunoreactivity (SPLI) in tissues of dog, rat and mouse. Acta Physiol. Scand. 112: 305–312, 1981.
 24. Burke, G. T., and T. Barka. Beta‐adrenergic receptors and adenylate cyclase in hypertrophic and hyperplastic rat salivary glands. Biochim. Biophys. Acta 539: 54–61, 1978.
 25. Butcher, F. R. The role of calcium and cyclic nucleotides in α‐amylase release from slices of rat parotid: studies with the divalent cation ionophore A‐23187. Metabolism 24: 409–418, 1975.
 26. Butcher, F. R. Calcium and cyclic nucleotides in the regulation of secretion from the rat parotid by autonomic agonists. In: Advances in Cyclic Nucleotide Research, edited by W. J. George and L. J. Ignarro. New York: Raven, 1978, vol. 9, p. 707–721.
 27. Butcher, F. R. Regulation of calcium efflux from isolated rat parotid cells. Biochim. Biophys. Acta 630: 254–260, 1980.
 28. Butcher, F. R., J. A. Goldman, and M. Nemerovski. Effect of adrenergic agents on α‐amylase release and adenosine 3'‐5'‐monophosphate accumulation in rat parotid tissue slices. Biochim. Biophys. Acta 392: 82–94, 1975.
 29. Butcher, F. R., P. A. McBride, and L. Rudich. Cholinergic regulation of cyclic nucleotide levels, amylase release, and K+ efflux from rat parotid glands. Mol. Cell. Endocrinol. 5: 243–254, 1976.
 30. Butcher, F. R., L. Rudich, C. Emler, and M. Nemerovski. Adrenergic regulation of cyclic nucleotide levels, amylase release and potassium efflux in rat parotid gland. Mol. Pharmacol. 12: 862–870, 1976.
 31. Butcher, F. R., M. Thayer, and J. A. Goldman. Effect of adenosine 3',5'‐cyclic monophosphate derivatives on α‐amylase release, protein kinase and cyclic nucleotide phosphodiesterase activity from rat parotid tissue. Biochim. Biophys. Acta 421: 289–295, 1976.
 32. Campos Gonzales, R., J. F. Whitfield, A. L. Boynton, J. P. MacManus, and R. H. Rixon. Prereplicative changes in the soluble calmodulin of isoproterenol‐activated rat parotid glands. J. Cell. Physiol. 118: 257–261, 1984.
 33. Carlsöö, B., A. Danielsson, and R. Henriksson. Effects of a new selective β1‐adrenoceptor agonist on amylase secretion from the rat parotid gland. Br. J. Pharmacol. 62: 364–366, 1978.
 34. Carlsöö, B., A. Danielsson, R. Henriksson, and L. A. Idahl. Characterization of the rat parotid β‐adrenoceptor. Br. J. Pharmacol. 72: 271–276, 1981.
 35. Carlsöö, B., A. Danielsson, R. Henriksson, and L. A. Idahl. Dissociation of β‐adrenoceptor‐induced effects on amylase secretion and cyclic adenosine 3',5'‐monophosphate accumulation. Br. J. Pharmacol. 75: 633–638, 1982.
 36. Cassel, D., and T. Pfeuffer. Mechanism of cholera toxin action: covalent modification of the guanyl nucleotide‐binding protein of the adenylate cyclase system. Proc. Natl. Acad. Sci. USA 75: 2669–2673, 1978.
 37. Davis, J. N., and W. Maury. Clonidine and related imidazolines are postsynaptic alpha adrenergic antagonists in dispersed rat parotid cells. J. Pharmacol. Exp. Ther. 207: 425–430, 1978.
 38. Dehaye, J. P., J. Christophe, F. Ernst, P. Poloczek, and P. Van Bogaert. Binding in vitro of vasoactive intestinal peptide on isolated acini of rat parotid glands. Arch. Oral Biol. 30: 827–832, 1985.
 39. Denton, R. M., and J. G. McCormack. Ca2+ transport by mammalian mitochondria and its role in hormone action. Am. J. Physiol. 249 (Endocrinol. Metab.12): E543–E554, 1985.
 40. Dormer, R. L., and S. J. Ashcroft. Studies on the role of calcium ions in the stimulation by adrenaline of amylase release from rat parotid. Biochem. J. 144: 543–550, 1974.
 41. Dowd, F. J., E. L. Watson, B. Horio, Y.‐S. Lau, and K. Park. Phosphorylation of rabbit parotid microsomal protein occurs only with β‐adrenergic stimulation. Biochem. Biophys. Res. Commun. 101: 281–288, 1981.
 42. Dreux, C., V. Imhoff, and B. Rossignol. Substance P as a modulator of β‐adrenergic regulation of protein secretion in rat parotid gland. In: Regulatory Peptides in Digestive, Nervous and Endocrine Systems. edited by M. J. M. Lewin and S. Bonfils. Amsterdam: Elsevier, 1985, p. 157–160. (INSERM Symp. 25.).
 43. Duncan, R., and E. H. McConkey. Preferential utilization of phosphorylated 40‐S ribosomal subunits during initiation complex formation. Eur. J. Biochem. 123: 535–538, 1982.
 44. Eckstein, F., S. Eimerl, and M. Schramm. Adenosine 3',5' cyclic phosphorothioate: an efficient inducer of amylase secretion in rat parotid slices. FEBS Lett. 64: 92–94, 1976.
 45. Ekström, J., and C. Wahlestedt. Supersensitivity to substance P and physalaemin in rat salivary glands after denervation or decentralization. Acta Physiol. Scand. 115: 437–446, 1982.
 46. Freedman, S. D., and J. D. Jamieson. Hormone‐induced protein phosphorylation. I. Relationship between secretagogue action and endogenous protein phosphorylation in intact cells from the exocrine pancreas and parotid. J. Cell Biol. 95: 903–908, 1982.
 47. Freedman, S. D., and J. D. Jamieson. Hormone‐induced protein phosphorylation. II. Localization to the ribosomal fraction from rat exocrine pancreas and parotid of a 29,000‐dalton protein phosphorylated in situ in response to secretagogues. J. Cell Biol. 95: 909–917, 1982.
 48. Freedman, S. D., and J. D. Jamieson. Hormone‐induced protein phosphorylation. III. Regulation of the phosphorylation of the secretagogue‐responsive 29,000‐dalton protein by both Ca2+ and cAMP in vitro. J. Cell Biol. 95: 918–923, 1982.
 49. Fuller, C. M., and D. V. Gallacher. β‐Adrenergic receptor mechanisms in rat parotid glands: activation by nerve stimulation and 3‐isobutyl‐1‐methylxanthine. J. Physiol. Lond. 356: 335–348, 1984.
 50. Gallacher, D. V. Substance P is a functional neurotransmitter in the rat parotid gland. J. Physiol. Lond. 342: 438–498, 1983.
 51. Gee, M. V., B. J. Baum, and G. S. Roth. Stimulation of parotid cell glucose oxidation. Role of alpha1‐adrenergic receptors and calcium mobilization. Biochem. Pharmacol. 32: 3351–3354, 1983.
 52. Gill, D. M., and R. Meren. ADP‐ribosylation of membrane proteins catalyzed by cholera toxin: basis of the activation of adenylate cyclase. Proc. Natl. Acad. Sci. USA 75: 3050–3054, 1978.
 53. Harfield, B., and A. Tenenhouse. Effect of EGTA on protein release and cyclic AMP accumulation in rat parotid gland. Can. J. Physiol. Pharmacol. 51: 997–1001, 1971.
 54. Hata, F., H. Ishida, K. Kagawa, E. Kondo, S. Kondo, and Y. Noguchi. β‐Adrenoceptor alterations coupled with secretory response in rat parotid tissue. J. Physiol. Lond. 341: 185–196, 1983.
 55. Hayakawa, M., H. Aoki, N. Terao, Y. Abiko, and H. Takiguchi. Vitamin D‐mediated decrease of Ca2+‐pump activity in the rat parotid gland. Int. J. Biochem. 15: 1175–1178, 1983.
 56. Henriksson, R. β1‐ And β2‐adrenoceptor agonists have different effects on rat parotid acinar cells. Am. J. Physiol. 242 (Gastrointest. Liver Physiol.5): G481–G485, 1982.
 57. Herman, G., S. Busson, L. Ovtracht, C. Maurs, and B. Rossignol. Regulation of protein discharge in two exocrine glands: rat parotid and exorbital lacrimal glands. Analogies between cholinergic (muscarinic) and α‐adrenergic stimulation and importance of extracellular calcium. Biol. Cell 31: 255–262, 1978.
 58. Hökfelt, T., O. Johannson, J.‐O. Kellerth, A. Ljungdahl, G. Nilsson, A. Nygards, and B. Pernow. Immuno‐histochemical distribution of substance P. In: Substance P, edited by U. S. von Euler and B. Pernow. New York: Raven, 1977, p. 117–145. (Nobel Symp. Ser. 37.).
 59. Hootman, S. R., T. M. Picado‐Leonard, and D. B. Burnham. Muscarinic acetylcholine receptor structure in acinar cells of mammalian exocrine glands. J. Biol. Chem. 260: 4186–4194, 1985.
 60. Inoue, Y., K. Kaku, T. Kaneko, N. Yanaihara, and T. Kanno. Vasoactive intestinal peptide binding to specific receptors on rat parotid acinar cells induces amylase secretion accompanied by intracellular accumulation of cyclic adenosine 3'‐5'‐monophosphate. Endocrinology 116: 686–692, 1985.
 61. Ishida, H., N. Miki, and H. Yoshida. Role of Ca2+ in the secretion of amylase from the parotid gland. Jpn. J. Pharmacol. 21: 227–238, 1971.
 62. Ito, H., M. T. Hoopes, B. J. Baum, and G. S. Roth. K+ release from rat parotid cells: an α1‐adrenergic mediated event. Biochem. Pharmacol. 31: 567–573, 1982.
 63. Jahn, R., and H. D. Söling. Phosphorylation of the same specific protein during amylase release evoked by β‐adrenergic or cholinergic agonists in rat and mouse parotid glands. Proc. Natl. Acad. Sci. USA 78: 6903–6906, 1981.
 64. Jahn, R., and H. D. Söling. Protein phosphorylation during secretion in the rat lacrimal gland. A general role of EC‐protein in stimulus‐secretion coupling in exocrine organs? FEBS Lett. 131: 28–30, 1981.
 65. Jahn, R., C. Unger, and H. D. Söling. Specific protein phosphorylation during stimulation of amylase secretion by β‐agonists or dibutyryl adenosine 3',5'‐monophosphate in the rat parotid gland. Eur. J. Biochem. 112: 345–352, 1980.
 66. Kanagasuntheram, P., and S. C. Lim. Parallel secretion of secretory proteins and calcium by the rat parotid gland. J. Physiol. Lond. 312: 445–454, 1981.
 67. Kanagasuntheram, P., and P. J. Randle. Calcium metabolism and amylase release in rat parotid acinar cells. Biochem. J. 160: 547–564, 1976.
 68. Kanagasuntheram, P., and T. S. Teo. Calmodulin‐sensitive ATP‐dependent calcium transport by the rat parotid endoplasmic reticulum. FEBS Lett. 141: 233–236, 1982.
 69. Kanagasuntheram, P., and T. S. Teo. Parotid microsomal Ca2+ transport. Subcellular localization and characterization. Biochem. J. 208: 789–794, 1982.
 70. Kanagasuntheram, P., and T. S. Teo. Does calmodulin mediate stimulus‐secretion coupling in the parotid gland? Studies using trifluoperazine. Biochem. Int. 7: 511–518, 1983.
 71. Kanamori, T., and T. Hayakawa. Cyclic AMP‐dependent 32P incorporation into a protein in rat parotid slices. Biochem. Int. 1: 395–402, 1980.
 72. Kanamori, T., and T. Hayakawa. Phosphorylation of the rat parotid Mr = 30,000 protein by cyclic AMP‐dependent protein kinase in a cell‐free system. Biochem. Int. 4: 39–46, 1982.
 73. Kanamori, T., T. Hayakawa, and T. Nagatsu. Adenosine 3',5'‐monophosphate‐dependent protein kinase and amylase secretion from rat parotid gland. Biochem. Biophys. Res. Commun. 57: 394–398, 1974.
 74. Kanamori, T., T. Hayakawa, and T. Nagatsu. Involvement of β1‐adrenergic receptors in regulation of the phosphorylation state of rat parotid gland proteins. Biomed. Res. 5: 77–82, 1984.
 75. Keller, P. J., M. Robinovitch, J. Iverson, and D. L. Kauffman. The protein composition of rat parotid saliva and secretory granules. Biochim. Biophys. Acta 379: 562–570, 1975.
 76. Keryer, G., and B. Rossignol. Effects of carbachol on extracellular Na‐dependent AIB uptake in rat parotid gland. Am. J. Physiol. 239 (Gastrointest. Liver Physiol.2): G183–G189, 1980.
 77. Kim, S.‐K. The cytochemical localization of adenylate cyclase activity in mucous and serous cells of the salivary gland. J. Supramol. Struct. 4: 185–197, 1976.
 78. Koelz, H. R., S. Kondo, A. L. Blum, and I. Schulz. Calcium ion uptake induced by cholinergic and α‐adrenergic stimulation in isolated cells of rat salivary glands. Pfluegers Arch. 370: 37–44, 1977.
 79. Kousvelari, E. E., S. R. Grant, D. K. Banerjee, M. J. Newby, and B. J. Baum. Cyclic AMP mediates β‐adrenergic‐induced increases in N‐linked protein glycosylation in rat parotid acinar cells. Biochem. J. 222: 17–24, 1984.
 80. Ku, K. Y., and F. R. Butcher. Detection of a calmodulin‐sensitive cyclic nucleotide phosphodiesterase in rat parotid gland. Biochim. Biophys. Acta 631: 70–78, 1980.
 81. Kusek, J. C. Amylase release from rat parotid glands. I. General characteristics. Biochim. Biophys. Acta 583: 295–308, 1979.
 82. Kusek, J. C. Amylase release from rat parotid glands. II. Calcium kinetics. Biochim. Biophys. Acta 583: 309–319, 1979.
 83. Leeson, C. R. Structure of salivary glands. In: Handbook of Physiology. Alimentary Canal, edited by C. F. Code. Washington, DC: Am. Physiol. Soc., 1967, sect. 6, vol. II, chapt. 32, p. 463–495.
 84. Leslie, B. A., J. W. Putney, Jr., and J. M. Sherman. α‐Adrenergic, β‐adrenergic and cholinergic mechanisms for amylase secretion by rat parotid gland in vitro. J. Physiol. Lond. 260: 351–370.
 85. Liang, T., and M. A. Cascieri. Substance P stimulation of amylase release by isolated parotid cells and inhibition of substance P induction of salivation by vasoactive peptides. Mol. Cell. Endocrinol. 15: 151–162, 1979.
 86. Liang, T., and M. A. Cascieri. Specific binding of an immunoreactive and biologically active 125I‐labeled N acylated substance P derivative to parotid cells. Biochem. Biophys. Res. Commun. 96: 1793–1799, 1980.
 87. Liang, T., and M. A. Cascieri. Substance P receptor on parotid cell membranes. J. Neurosci. 1: 1133–1141, 1981.
 88. Lindsay, R. H., T. Ueha, B. S. Hulsey, and R. W. Hanson. Relationship of chemically initiated enzyme secretion to metabolism in rat parotid in vitro. Am. J. Physiol. 221: 80–85, 1971.
 89. Ludford, J. M., and B. R. Talamo. β‐Adrenergic and muscarinic receptors in developing rat parotid glands. Selective effect of neonatal sympathetic denervation. J. Biol. Chem. 255: 4619–4627, 1980.
 90. McPherson, M. A., and C. N. Hales. Control of amylase biosynthesis and release in the parotid gland of the rat. Biochem. J. 176: 855–863, 1978.
 91. Michell, R. H., and L. M. Jones. Enhanced phosphatidylinositol labelling in rat parotid fragments exposed to α‐adrenergic stimulation. Biochem. J. 138: 47–52, 1974.
 92. Miller, B. E., and D. L. Nelson. Calcium fluxes in isolated acinar cells from rat parotid. Effect of adrenergic and cholinergic stimulation. J. Biol. Chem. 252: 3629–3636, 1977.
 93. Mori, T., Y. Takai, R. Minakuchi, B. Yu, and Y. Nishizuka. Inhibitory action of chlorpromazine, dibucaine, and other phospholipid‐interacting drugs on calcium‐activated, phospholipid‐dependent protein kinase. J. Biol. Chem. 255: 8378–8380, 1980.
 94. Nicholls, D. G., and M. Crompton. Mitochondrial calcium transport. FEBS Lett. 111: 261–268, 1980.
 95. Ohshika, H., H. Takemura, J. Endo, S. Hatta, and M. Tanaka. Stimulating effect of α‐adrenoceptor agonists on isoproterenol‐induced amylase release in rat parotid tissue. Jpn. J. Pharmacol. 31: 1021–1027, 1981.
 96. Oron, Y., S. Creacy, J. Kellogg, and J. Larner. Stable cholinergic‐muscarinic and α‐adrenergic inhibition of rat parotid adenylate cyclase. J. Cyclic Nucleotide Res. 6: 105–120, 1980.
 97. Oron, Y., J. Kellogg, and J. Larner. Alpha adrenergic and cholinergic‐muscarinic regulation of adenosine cyclic 3',5'‐monophosphate levels in the rat parotid. Mol. Pharmacol. 14: 1018–1030, 1978.
 98. Oron, Y., M. Lowe, and Z. Selinger. Involvement of the α‐adrenergic receptor in the phospholipid effect in rat parotid. FEBS Lett. 34: 198–200, 1973.
 99. Oron, Y., M. Lowe, and Z. Selinger. Incorporation of inorganic [32P]phosphate into rat parotid phosphatidylinositol. Induction through activation of alpha adrenergic and cholinergic receptors and relation to K+ release. Mol. Pharmacol. 11: 79–86, 1975.
 100. Padel, U., J. Kruppa, R. Jahn, and H. D. Söling. Phosphopeptide patterns of the ribosomal protein S6 following stimulation of guinea pig parotid glands by secretagogues involving either cAMP or calcium as second messenger. FEBS Lett. 159: 112–118, 1983.
 101. Padel, U., and H. D. Söling. Phosphorylation of the ribosomal protein S6 during agonist‐induced exocytosis in exocrine glands is catalyzed by calcium‐phospholipid‐dependent protein kinase (protein kinase C). Experiments with guinea pig parotid glands. Eur. J. Biochem. 151: 1–10, 1985.
 102. Plewe, G., R. Jahn, A. Immelmann, C. Bode, and H. D. Söling. Specific phosphorylation of a protein in calcium accumulating endoplasmic reticulum from rat parotid glands following stimulation by agonists involving cAMP as second messenger. FEBS Lett. 166: 96–103, 1984.
 103. Putney, J. W.,Jr. On the role of cellular calcium in the response of the parotid to dibutyryl and monobutyryl cyclic AMP. Life Sci. 22: 631–638, 1978.
 104. Putney, J. W.,Jr. Oxygen consumption in the parotid gland. Life Sci. 22: 1731–1736, 1978.
 105. Putney, J. W.,Jr., J. S. McKinney, D. L. Aub, and B. A. Leslie. Phorbol ester‐induced protein secretion in rat parotid gland. Relationship to the role of inositol lipid breakdown and protein kinase C activation in stimulus‐secretion coupling. Mol. Pharmacol. 26: 261–266, 1984.
 106. Putney, J. W., Jr., and C. M. Van de Walle. The relationship between muscarinic receptor binding and ion movements in rat parotid cells. J. Physiol. Lond. 299: 521–531, 1980.
 107. Putney, J. W.,Jr., C. M. Van de Walle, and B. A. Leslie. Receptor control of calcium influx in parotid acinar cells. Mol. Pharmacol. 14: 1046–1053, 1978.
 108. Putney, J. W.,Jr., C. M. Van de Walle, and C. S. Wheeler. Binding of 125I‐physalaemin to rat parotid acinar cells. J. Physiol. Lond. 301: 205–212, 1980.
 109. Putney, J. W.,Jr., S. J. Weiss, B. A. Leslie, and S. H. Marier. Is calcium the final mediator of exocytosis in the rat parotid gland? J. Pharmacol. Exp. Ther. 203: 144–155, 1977.
 110. Quissell, D. O., L. M. Deisher, and K. A. Barzen. Role of protein phosphorylation in regulating rat submandibular mucin secretion. Am. J. Physiol. 245 (Gastrointest. Liver Physiol.8): G44–G53, 1983.
 111. Quissell, D. O., J. L. Lafferty, and K. A. Barzen. Dispersed rat parotid cells: role of calcium and cAMP in the regulation of amylase release. J. Dent. Res. 62: 131–134, 1983.
 112. Robinovitch, M. R., and L. M. Sreebny. Separation and identification of some of the protein components of rat parotid saliva. Arch. Oral Biol. 14: 935–939, 1969.
 113. Rossignol, B., G. Herman, A. M. Chambaut, and G. Keryer. The calcium ionophore A23187 as a probe for studying the role of Ca2+ ions in the mediation of carbachol effects in rat salivary glands: protein secretion and metabolism of phospholipids and glycogen. FEBS Lett. 43: 241–246, 1974.
 114. Rudich, L., and F. R. Butcher. Effect of substance P and eledoisin on K+ efflux, amylase release and cyclic nucleotide levels in slices of rat parotid gland. Biochim. Biophys. Acta 444: 704–711, 1976.
 115. Sampson, H. W., D. J. Kiessel, L. Mackenzie‐Graham, and I. Piscopo. A cytochemical study of the effect of cholinergic and β‐adrenergic stimulation on calcium fluxes of rat parotid gland. Histochemistry 79: 193–203, 1983.
 116. Scarpa, A., K. Malmstrom, M. Chiesi, and E. Carafoli. On the problem of the release of mitochondrial calcium by cyclic AMP. J. Membr. Biol. 29: 205–208, 1976.
 117. Schneyer, L. H., J. A. Young, and C. A. Schneyer. Salivary secretion of electrolytes. Physiol. Rev. 52: 720–777, 1972.
 118. Schramm, M., and E. Naim. Adenyl cyclase of rat parotid gland. Activation by fluoride and norepinephrine. J. Biol. Chem. 245: 3225–3231, 1970.
 119. Schramm, M., and Z. Selinger. The function of α‐ and β‐adrenergic receptors and a cholinergic receptor in the secretory cell of rat parotid gland. In: Advances in Cytopharmacology, edited by B. Ceccarelli, F. Clementi, and J. Meldolesi. New York: Raven, 1974, vol. 2, p. 29–32.
 120. Scott, B. L., and D. C. Pease. Electron microscopy of the salivary gland and lacrimal glands of the rat. Am. J. Anat. 104: 115–161, 1959.
 121. Scott, J., and B. J. Baum. Involvement of cyclic AMP and calcium in exocrine protein secretion induced by vasoactive intestinal polypeptide in rat parotid cells. Biochim. Biophys. Acta 847: 255–262, 1985.
 122. Seamon, K., and J. W. Daly. Activation of adenylate cyclase by the diterpene forskolin does not require the guanine nucleotide regulatory protein. J. Biol. Chem. 256: 9799–9801, 1981.
 123. Selinger, Z., and E. Naim. The effect of calcium on amylase secretion by rat parotid slices. Biochim. Biophys. Acta 203: 335–337, 1970.
 124. Selinger, Z., E. Naim, and M. Lasser. ATP‐dependent calcium uptake by microsomal preparations from rat parotid and submaxillary glands. Biochim. Biophys. Acta 203: 326–334, 1970.
 125. Spearman, T. N., and F. R. Butcher. Rat parotid gland protein kinase activation. Relationship to enzyme secretion. Mol. Pharmacol. 21: 121–127, 1982.
 126. Spearman, T. N., and F. R. Butcher. The effect of calmodulin antagonists on amylase release from the rat parotid gland in vitro. Pfluegers Arch. 397: 220–224, 1983.
 127. Spearman, T. N., J. P. Durham, and F. R. Butcher. The role of cyclic AMP in the regulation of exocytosis in the rat parotid gland: evidence obtained with the isoproterenol analog PI‐39. J. Cyclic Nucleotide Res. 8: 225–234, 1982.
 128. Spearman, T. N., J. P. Durham, and F. R. Butcher. Cyclic AMP in the regulation of exocytosis in the rat parotid gland. Evidence obtained with cholera toxin. Biochim. Biophys. Acta 759: 117–124, 1983.
 129. Spearman, T. N., K. P. Hurley, R. Olivas, R. G. Ulrich, and F. R. Butcher. Subcellular location of stimulus‐affected endogenous phosphoproteins in the rat parotid gland. J. Cell Biol. 99: 1354–1363, 1984.
 130. Stengel, D., L. Guenet, M. Desmier, P. Insel, and J. Hanoune. Forskolin requires more than the catalytic unit to activate adenylate cyclase. Mol. Cell. Endocrinol. 28: 681–690, 1982.
 131. Strittmatter, W. J., J. N. Davis, and R. J. Lefkowitz. α‐Adrenergic receptors in rat parotid cells. I. Correlation of [3H]dihydroergocryptine binding and catecholamine‐stimulated potassium efflux. J. Biol. Chem. 252: 5472–5477, 1977.
 132. Sundström, S., B. Carlsöö, A. Danielsson, and R. Henriksson. Differences in dopamine‐ and noradrenaline‐induced amylase release from the rat parotid gland. Eur. J. Pharmacol. 109: 355–361, 1985.
 133. Takemura, H. Inhibitory effect of carbachol on isoproterenol‐induced amylase release from isolated rat parotid cells. Jpn. J. Pharmacol. 35: 9–17, 1984.
 134. Takemura, H. Potentiation of amylase release from isolated rat parotid cells—studies on the combination of isoproterenol and a low dose of carbachol. Jpn. J. Pharmacol. 36: 107–109, 1984.
 135. Takemura, H. Changes in cytosolic free calcium concentration in isolated rat parotid cells by cholinergic and β‐adrenergic agonists. Biochem. Biophys. Res. Commun. 131: 1048–1055, 1985.
 136. Takuma, T., B. L. Kuyatt, and B. J. Baum. Calcium transport mechanisms in basolateral plasma membrane‐enriched vesicles from rat parotid gland. Biochem. J. 227: 239–245, 1985.
 137. Templeton. D. Augmented amylase release from rat parotid gland slices, in vitro. Pfluegers Arch. 384: 287–289, 1980.
 138. Tsang, B. K., R. H. Rixon, and J. F. Whitfield. A possible role for cyclic AMP in the initiation of DNA synthesis by isoproterenol‐activated parotid gland cells. J. Cell. Physiol. 102: 19–26, 1980.
 139. von Zastrow, M., T. R. Tritton, and J. D. Castle. Identification of L‐ascorbic acid in secretion granules of the rat parotid gland. J. Biol. Chem. 259: 11746–11750, 1984.
 140. Wallach, D., and M. Schramm. Calcium and the exportable protein in the rat parotid gland. Parallel subcellular distribution and concomitant secretion. Eur. J. Biochem. 21: 433–437, 1971.
 141. Wharton, J., J. M. Polack, M. G. Bryant, S. Van Noorden, S. R. Bloom, and A. G. E. Pearse. Vasoactive intestinal polypeptide (VIP)‐like immunoreactivity in salivary glands. Life Sci. 25: 273–280, 1979.
 142. Wilchek, M., Y. Salomon, M. Lowe, and Z. Selinger. Conversion of protein kinase to a cyclic AMP independent form by affinity chromatography on N6‐caproyl 3',5'‐cyclic adenosine monophosphate‐Sepharose. Biochem. Biophys. Res. Commun. 45: 1177–1184, 1971.
 143. Williamson, J. R., R. H. Cooper, and J. B. Hoek. Role of calcium in the hormonal regulation of liver metabolism. Biochim. Biophys. Acta 639: 243–295, 1981.
 144. Yokoyama, N., M. Abe, and S. Furuyama. Cyclic nucleotide phosphodiesterase in rat parotid gland. Can. J. Physiol. Pharmacol. 59: 293–299, 1981.
 145. Yoshimura, K., E. Nezu, and A. Chiba. Stimulation of α‐amylase release and cyclic AMP accumulation by catecholamine in rat parotid slices in vitro. Jpn. J. Physiol. 32: 121–135, 1982.
 146. Yoshimura, K., E. Nezu, and T. Yoneyama. Stimulation of cyclic AMP‐dependent protein kinase by catecholamines and its relationship to α‐amylase release in rat parotid gland. Jpn. J. Physiol. 32: 699–716, 1982.
 147. Yoshimura, K., E. Nezu, and T. Yoneyama. Mechanism of regulation of amylase release by α‐ and β‐adrenergic agonists in rat parotid tissue. Jpn. J. Physiol. 34: 665–667, 1984.
 148. Yoshimura, K., E. Nezu, and T. Yoneyama. Augmentation of isoproterenol‐stimulated tissue cyclic AMP level by cholinergic agonists in rat parotid gland. Jpn. J. Physiol. 35: 765–781, 1985.

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Terry N. Spearman, Fred R. Butcher. Cellular Regulation of Amylase Secretion by the Parotid Gland. Compr Physiol 2011, Supplement 18: Handbook of Physiology, The Gastrointestinal System, Salivary, Gastric, Pancreatic, and Hepatobiliary Secretion: 63-77. First published in print 1989. doi: 10.1002/cphy.cp060304