Abstract
1 The mechanism by which dibutyryl cyclic adenosine-3'-5'-monophosphate (dibutyryl cyclic AMP) potentiates the secretory effect of carbachol in rat exocrine pancreas was investigated. 2 Dibutyryl cyclic AMP potentiated the secretory effect of carbachol only at carbachol concentrations greater than or equal to 10(-7) mol/l; was independent of carbachol at concentrations greater than 10(-7) mol/l and was inversely proportional to extracellular [Ca2+]. 3 Carbachol increased and dibutyryl cyclic AMP reduced the rate of 45Ca efflux from the tissue. 4 A-23187 stimulated 3H-protein release in the presence of Ca2+ and this effect was potentiated by dibutyryl cyclic AMP; the degree of potentiation was inversely proportional to extracellular [Ca2+]. At 10(-3) mol/l [Ca2+] the potentiation occurred only at ionophore concentrations less than or equal to 10(-6) mol/litre. 5 These results support the hypothesis that dibutyryl cyclic AMP potentiates the effect of secretagogues in rat exocrine pancreas by maintaining an elevated intracellular calcium concentration. It does so by inhibiting Ca2+ efflux. The results also suggest that the limiting factor in carbachol-stimulated secretion, at all concentrations of carbachol, is intracellular [Ca2+].
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Selected References
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- Benz L., Eckstein B., Matthews E. K., Williams J. A. Control of pancreatic amylase release in vitro: effects of ions, cyclic AMP, and colchicine. Br J Pharmacol. 1972 Sep;46(1):66–67. doi: 10.1111/j.1476-5381.1972.tb06849.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Borle A. B. Calcium metabolism at the cellular level. Fed Proc. 1973 Sep;32(9):1944–1950. [PubMed] [Google Scholar]
- Borle A. B. Cyclic AMP stimulation of calcium efflux from kidney, liver and heart mitochondria. J Membr Biol. 1974;16(3):221–236. doi: 10.1007/BF01872416. [DOI] [PubMed] [Google Scholar]
- Case R. M., Clausen T. The relationship between calcium exchange and enzyme secretion in the isolated rat pancreas. J Physiol. 1973 Nov;235(1):75–102. doi: 10.1113/jphysiol.1973.sp010379. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Case R. M., Scratcherd T. The actions of dibutyryl cyclic adenosine 3',5'-monophosphate and methyl xanthines on pancreatic exocrine secretion. J Physiol. 1972 Jun;223(3):649–667. doi: 10.1113/jphysiol.1972.sp009867. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Douglas W. W. Stimulus-secretion coupling: the concept and clues from chromaffin and other cells. Br J Pharmacol. 1968 Nov;34(3):451–474. doi: 10.1111/j.1476-5381.1968.tb08474.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- EAGLE H. Amino acid metabolism in mammalian cell cultures. Science. 1959 Aug 21;130(3373):432–437. doi: 10.1126/science.130.3373.432. [DOI] [PubMed] [Google Scholar]
- Eimerl S., Savion N., Heichal O., Selinger Z. Induction of enzyme secretion in rat pancreatic slices using the ionophore A-23187 and calcium. An experimental bypass of the hormone receptor pathway. J Biol Chem. 1974 Jun 25;249(12):3991–3993. [PubMed] [Google Scholar]
- Goldberg N. D., O'Dea R. F., Haddox M. K. Cyclic GMP. Adv Cyclic Nucleotide Res. 1973;3:155–223. [PubMed] [Google Scholar]
- Heisler S., Fast D., Tenenhouse A. Role of Ca 2+ and cyclic AMP in protein secretion from rat exocrine pancreas. Biochim Biophys Acta. 1972 Oct 25;279(3):561–572. doi: 10.1016/0304-4165(72)90178-x. [DOI] [PubMed] [Google Scholar]
- Heisler S., Grondin G. Effect of lanthanum on 45Ca flux and secretion of protein from rat exocrine pancreas. Life Sci. 1973 Oct 1;13(7):783–794. doi: 10.1016/0024-3205(73)90069-6. [DOI] [PubMed] [Google Scholar]
- Hokin L. E. Effects of calcium omission on acetylcholine-stimulated amylase secretion and phospholipid synthesis in pigeon pancreas slices. Biochim Biophys Acta. 1966 Jan 25;115(1):219–221. doi: 10.1016/0304-4165(66)90066-3. [DOI] [PubMed] [Google Scholar]
- Jamieson J. D., Palade G. E. Intracellular transport of secretory proteins in the pancreatic exocrine cell. I. Role of the peripheral elements of the Golgi complex. J Cell Biol. 1967 Aug;34(2):577–596. doi: 10.1083/jcb.34.2.577. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Matthews E. K., Petersen O. H., Williams J. A. Pancreatic acinar cells: acetylcholine-induced membrane depolarization, calcium efflux and amylase release. J Physiol. 1973 Nov;234(3):689–701. doi: 10.1113/jphysiol.1973.sp010367. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rasmussen H. Cell communication, calcium ion, and cyclic adenosine monophosphate. Science. 1970 Oct 23;170(3956):404–412. doi: 10.1126/science.170.3956.404. [DOI] [PubMed] [Google Scholar]
- Rasmussen H., Goodman D. B., Tenenhouse A. The role of cyclic AMP and calcium in cell activation. CRC Crit Rev Biochem. 1972 Feb;1(1):95–148. doi: 10.3109/10409237209102545. [DOI] [PubMed] [Google Scholar]
- Rasmussen H., Tenenhouse A. Cyclic adenosine monophosphate, CA++, and membranes. Proc Natl Acad Sci U S A. 1968 Apr;59(4):1364–1370. doi: 10.1073/pnas.59.4.1364. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reed P. W., Lardy H. A. A23187: a divalent cation ionophore. J Biol Chem. 1972 Nov 10;247(21):6970–6977. [PubMed] [Google Scholar]
- Robberecht P., Christophe J. Secretion of hydrolases by perfused fragments of rat pancreas: effect of calcium. Am J Physiol. 1971 Apr;220(4):911–917. doi: 10.1152/ajplegacy.1971.220.4.911. [DOI] [PubMed] [Google Scholar]
- Robberecht P., Deschodt-Lanckman M., De Neef P., Borgeat P., Christophe J. In vivo effects of pancreozymin, secretin, vasoactive intestinal polypeptide and pilocarpine on the levels of cyclic AMP and cyclic GMP in the rat pancreas. FEBS Lett. 1974 Jul 15;43(2):139–143. doi: 10.1016/0014-5793(74)80986-5. [DOI] [PubMed] [Google Scholar]
- Williams J. A., Lee M. Pancreatic acinar cells: use of Ca++ ionophore to separate enzyme release from the earlier steps in stimulus-secretion coupling. Biochem Biophys Res Commun. 1974 Sep 23;60(2):542–548. doi: 10.1016/0006-291x(74)90274-5. [DOI] [PubMed] [Google Scholar]
