Abstract
Isolated canine parietal cells were used to study the ability of misoprostol to inhibit acid secretion in the presence of a number of acid secretagogues. Misoprostol inhibited histamine-stimulated acid secretion in a dose-dependent and noncompetitive manner. A concentration of 2–3×10−9 M misoprostol inhibited maximal histamine-stimulated acid secretion by one half. Misoprostol had little to no effect on acid secretion stimulated by carbachol and dibutyryl cAMP, had no effect on the acid secretion directly stimulated by pentagastrin, and only modestly inhibited acid secretion stimulated by forskolin. Misoprostol noncompetitively inhibited cAMP formation in response to histamine, with an IC50 value similar to that for the inhibition of histamine-stimulated acid secretion. These results indicate that: (1) misoprostol specifically inhibits histamine-stimulated acid secretion in parietal cells, and (2) the antisecretory action of misoprostol is closely related to the reduction of histamine-stimulated cAMP formation with the site of major action most likely in the coupling process between histamine H2 receptor sites and histamine-sensitive adenylate cyclase.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Robert A: Antisecretory, antiulcer, cytoprotective and diarrheogenic properties of prostaglandins.In Advances in Prostaglandin and Thromboxane Research. B Samuelsson, R Paoletti (eds). Raven Press, New York, 1976, pp 507–520
Robert A: Cytoprotection by prostaglandins. Gastroenterology 77:761–767, 1979
Brand DL, Roufail WM, Thomson ABR, Tapper, EJ: Misoprostol, a synthetic PGE1 analog, in the treatment of duodenal ulcers. Dig Dis Sci 30(suppl):147S-158S, 1985
Sontag SJ, Mazure PA, Pontes JF, Beker SG, Dajani EZ: Misoprostol in the treatment of duodenal ulcer. Dig Dis Sci 30(supll):159S-163S, 1985
Nicholson PA: A multicenter international controlled comparison of two dosage regimes of misoprostol and cimetidine in the treatment of duodenal ulcer in out-patients. Dig Dis Sci 30(suppl):171S-177S, 1985
Dajani EZ, Driskill DR, Bianchi RG, Collins PW: Comparative gastric antisecretory and antiulcer effects of prostaglandin E1 and its methyl ester in animals. Prostaglandins 10:205–215, 1975
Bauer RF, Bianchi RG, Casler J, Goldstin B: Comparative mucosal protective properties of misoprostol, cimetidine, and sucralfate. Dig Dis Sci 31(suppl):81S-85S, 1986
Colton DG, Driskill DR, Dajani EZ: Effects of a prostaglanding E1 derivative, SC-29333, and aspirin on gastric ionic fluxes and potential difference in dog. J Pharmacol Exp Ther 210:283–288, 1979
Collins PW, Dajani EZ, Pappo R, Gasiecki AF, Bianchi RG, Woods EM: Synthesis and gastric antisecretory properties of 4,5-unsaturated derivatives of 15-deoxy-16-hydroxy-16-methyl prostaglandin E1. J Med Chem 26:786–790, 1983
Collins PW, Pappo R, Dajani EZ: Chemistry and synthetic development of misoprostol. Dig Dis Sci 30(suppl): 114S-117S, 1985
Soll AH: The actions of secretagogues on oxygen uptake by isolated mammalian parietal cells. J Clin Invest 61:370–380, 1978
Skoglund ML, Nies AS, Gerber JG: Inhibition of acid secretion in isolated canine parietal cells by prostaglandins. J Pharmacol Exp Ther 220:371–374, 1982
Berglindh T, Helander HF, Obrink KJ: Effects of secretagogues on oxygen consumption, aminopyrine accumulation and morphology in isolated gastric glands. Acta physiol Scand 97:401–414, 1976
Soll AH: Secretagogue stimulation of [14C]aminopyrine accumulation by isolated canine parietal cells. Am J Physiol 238(Gastrointest Liver Physiol 1):G366-G375, 1980
Soll AH: Specific inhibition by prostaglandin E2 and I2 of histamine-stimulated [14C]aminopyrine accumulation and cyclic adenosine monophosphate generation by isolated canine parietal cells. J Clin Invest 65:1222–1229, 1980
Seamon KB, Daly JW: Forskolin: A unique diterpene activator of cylic AMP-generating systems. J Cyclic Nucleotide Res 7:201–224, 1981
Seamon KB, Padgett W, Daly JW: Forskolin: A unique diterpene activator of adenylate cyclase in membranes and intact cells. Proc Natl Acad Sci USA 78:3363–3367, 1981
Soll AH, Whittle BJR: Prostacyclin analogues inhibit canine parietal cell activity and cAMP formation. Prostaglandins 21:353–365, 1981
Chew CS: Forskolin stimulation of acid and pepsinogen secretion in isolated gastric glands. Am J Physiol 245(Cell Physiol 14):C371-C380, 1983
Soll AH: The interaction of histamine with gastrin and carbamylcholine on oxygen uptake by isolated mammalian parietal cells. J Clin Invest 61:381–389, 1978
Chew CS, Hersey SJ: Gastrin stimulation of isolated gastric glands. Am J Physiol 242 (Gastrointest Liver Physiol 5): G504-G512, 1982
Hirschowitz BI, Gibson RG: Effect of cimetidine on stimulated gastric secretion and serum gastrin in the dog. Am J Gastroenterol 70:437–447, 1978
Bajaj SC, Hirschowitz BI: Inhibition of basal and stimulated gastric H+ and pepsin secretion in duodenal ulcer patients by an H2 histamine antagonist. Am J Dig Dis 21:557–562, 1976
Konturek SJ, Biernat J, Olesky J: Effect of metiamide H2 receptor antagonists on gastric response to histamine, pentagastrin, insulin and peptone meal in man. Am J Dig Dis 19:609–616, 1974
Mainardi M, Maxwell V, Sturdevant RAL, Isenberg JI: Inhibition of gastric acid secretion in duodenal ulcer patients N Engl J Med 291:373–376, 1974
Major JS, Scholes P: The localization of a histamine H2 receptor adenylate cyclase system in canine parietal cells and its inhibition by prostaglandins. Agents Actions 8:324–331, 1978
Soll AH, Wollin, A: Histamine and cyclic AMP in isolated canine parietal cells. Am J Physiol 237(5):E444-E450, 1979
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Tsai, B.S., Kessler, L.K., Butchko, G.M. et al. Effect of misoprostol on histamine-stimulated acid secretion and cyclic AMP formation in isolated canine parietal cells. Digest Dis Sci 32, 1010–1016 (1987). https://doi.org/10.1007/BF01297192
Received:
Revised:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF01297192