Skip to main content
PMC home page
The Journal of Clinical Investigation logoLink to The Journal of Clinical Investigation
. 1976 Jun;57(6):1548–1553. doi: 10.1172/JCI108425

Interaction of prostaglandins and histamine with enzymes of cyclic AMP metabolism from guinea pig gastric mucosa.

A Wollin, C F Code, T P Dousa
PMCID: PMC436814  PMID: 180055

Abstract

Prostaglandins (PGE1, PGE2, PGA1) and histamine have opposing effects on gastric HCl secretion, but we found that both stimulate adenylate cyclase activity in cell-free membrane preparations of guinea pig gastric fundic mucosa. The stimulatory effect of prostaglandins was found in this study to be specific and dose-dependent over a concentration range from 10(-7) to 10(-4) M. In similar preparations from antral regions of guinea pig gastric mucosa, the adenylate cyclase was stimulated only by PGE1, PGE2, and PGA1 and not by histamine. Maximum stimulating doses of PGE1, PGE2, or PGA1, and of histamine had an additive effect on the adenylate cyclase activity from fundic gastric mucosa. Metiamide, a histamine H2-receptor antagonist, inhibited the stimulation of fundic mucosa adenylate cyclase by histamine but did not interfere with the stimulation by prostaglandins. Cyclic AMP phosphodiesterase activity of guinea pig gastric mucosa was unaffected by PGE1 and PGE2 or by histamine, and was slightly depressed by PGA1. These results indicate that histamine and prostaglandins stimulate two different adenylate cyclase systems both present in guinea pig gastric mucosa tissue. Therefore, the known inhibitory effect of prostaglandins on gastric acid secretion is not related to the interference with the stimulation of the histamine H2-receptor-sensitive adenylate cyclase complex by histamine nor do prostaglandins accelerate cyclic AMP breakdown by cyclic AMP phosphodiesterase to reduce cyclic AMP levels.

Full text

PDF
1552

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bersimbaev R. I., Argutinskaya S. V., Salganik R. I. The stimulating action of gastrin pentapeptide and histamine on adenyl cyclase activity in rat stomach. Experientia. 1971 Dec 15;27(12):1389–1390. doi: 10.1007/BF02154246. [DOI] [PubMed] [Google Scholar]
  2. Bieck P. R., Oates J. A., Robison G. A., Adkins R. B. Cyclic AMP in the regulation of gastric secretion in dogs and humans. Am J Physiol. 1973 Jan;224(1):158–164. doi: 10.1152/ajplegacy.1973.224.1.158. [DOI] [PubMed] [Google Scholar]
  3. Black J. W., Duncan W. A., Durant C. J., Ganellin C. R., Parsons E. M. Definition and antagonism of histamine H 2 -receptors. Nature. 1972 Apr 21;236(5347):385–390. doi: 10.1038/236385a0. [DOI] [PubMed] [Google Scholar]
  4. Dousa T. P., Code C. F. Effect of histamine and its methyl derivatives on cyclic AMP metabolism in gastric mucosa and its blockade by an H2 receptor antagonist. J Clin Invest. 1974 Jan;53(1):334–337. doi: 10.1172/JCI107555. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dousa T., Hechter O., Schwartz I. L., Walter R. Neurohypophyseal hormone-responsive adenylate cyclase from mammalian kidney. Proc Natl Acad Sci U S A. 1971 Aug;68(8):1693–1697. doi: 10.1073/pnas.68.8.1693. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Grossman M. I., Konturek S. J. Inhibition of acid secretion in dog by metiamide, a histamine antagonist acting on H2 receptors. Gastroenterology. 1974 Apr;66(4):517–521. [PubMed] [Google Scholar]
  7. Karppanen H. O., Neuvonen P. J., Bieck P. R., Westermann E. Effect of histamine, pentagastrin and theophylline on the production of cyclic AMP in isolated gastric tissue of the guinea pig. Naunyn Schmiedebergs Arch Pharmacol. 1974;284(1):15–23. doi: 10.1007/BF00499969. [DOI] [PubMed] [Google Scholar]
  8. Katsumata Y., Glick D. Effects of drugs influencing gastric secretion on the quantitative histological distribution of cyclic adenosine 3':5'-monophosphate in the rat stomach. Gastroenterology. 1975 Aug;69(2):409–415. [PubMed] [Google Scholar]
  9. Kimbert D. V. Cyclic nucleotides and their role in gastrointestinal secretion. Gastroenterology. 1974 Nov;67(5):1023–1064. [PubMed] [Google Scholar]
  10. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  11. Main I. H., Whittle B. J. Prostaglandin E2 and the stimulation of rat gastric acid secretion by dibutyryl cyclic 3',5'-AMP. Eur J Pharmacol. 1974 May;26(2):204–211. doi: 10.1016/0014-2999(74)90229-5. [DOI] [PubMed] [Google Scholar]
  12. McKenzie S. G., Bär H. P. On the mechanism of adenyl cyclase inhibition by adenosine. Can J Physiol Pharmacol. 1973 Mar;51(3):190–196. doi: 10.1139/y73-027. [DOI] [PubMed] [Google Scholar]
  13. McNeil J. H., Verma S. C. Stimulation of rat gastric adenylate cyclase by histamine and histamine analogues and blockade by burimamide. Br J Pharmacol. 1974 Sep;52(1):104–106. doi: 10.1111/j.1476-5381.1974.tb09694.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Nakajima S., Hirschowitz B. I., Sachs G. Studies on adenyl cyclase in Necturus gastric mucosa. Arch Biochem Biophys. 1971 Mar;143(1):123–126. doi: 10.1016/0003-9861(71)90191-3. [DOI] [PubMed] [Google Scholar]
  15. Nezamis J. E., Robert A., Stowe D. F. Inhibition by prostaglandin E 1 of gastric secretion in the dog. J Physiol. 1971 Oct;218(2):369–383. doi: 10.1113/jphysiol.1971.sp009623. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Preiss D. U., Code C. F. Effect of the H2-receptor antagonists (burimamide and metiamide) on gastric secretion stimulated by histamine and its methyl derivatives. J Pharmacol Exp Ther. 1975 May;193(2):614–620. [PubMed] [Google Scholar]
  17. Ray T. K., Forte J. G. Adenyl cyclase of oxyntic cells. Its association with different cellular membranes. Biochim Biophys Acta. 1974 Sep 23;363(3):320–339. doi: 10.1016/0005-2736(74)90072-8. [DOI] [PubMed] [Google Scholar]
  18. Sung C. P., Jenkins B. C., Burns L. R., Hackney V., Spenney J. G., Sachs G., Wiebelhaus V. D. Adenyl and guanyl cyclase in rabbit gastric mucosa. Am J Physiol. 1973 Dec;225(6):1359–1363. doi: 10.1152/ajplegacy.1973.225.6.1359. [DOI] [PubMed] [Google Scholar]
  19. Sung C. P., Wiebelhaus V. D., Jenkins B. C., Adlercreutz P., Hirschowitz B. I., Sachs G. Heterogeneity of 3',5'-phosphodiesterase of gastric mucosa. Am J Physiol. 1972 Sep;223(3):648–650. doi: 10.1152/ajplegacy.1972.223.3.648. [DOI] [PubMed] [Google Scholar]
  20. Thompson W. J., Appleman M. M. Multiple cyclic nucleotide phosphodiesterase activities from rat brain. Biochemistry. 1971 Jan 19;10(2):311–316. [PubMed] [Google Scholar]
  21. Way L., Durbin R. P. Inhibition of gastric acid secretion in vitro by prostaglandin E1. Nature. 1969 Mar 1;221(5183):874–875. doi: 10.1038/221874a0. [DOI] [PubMed] [Google Scholar]
  22. Whittle B. J. Studies on the mode of action of cyclic 3'5'-AMP and prostaglndin E 2 on rat gastric acid secretion and mucosal blood flow. Br J Pharmacol. 1972 Nov;46(3):546P–547P. [PMC free article] [PubMed] [Google Scholar]
  23. Wilson D. E., Winnan G., Quertermus J., Tao P. Effects of an orally administered prostaglandin analogue (16, 16-dimethyl prostaglandin E2) on human gastric secretion. Gastroenterology. 1975 Sep;69(3):607–611. [PubMed] [Google Scholar]
  24. Wollin A., Barnes L. D., Hui Y. S., Dousa T. P. Activation of protein kinase in the guinea pig fundic gastric mucosa by histamine. Life Sci. 1975 Oct 15;17(8):1303–1306. doi: 10.1016/0024-3205(75)90142-3. [DOI] [PubMed] [Google Scholar]

Articles from Journal of Clinical Investigation are provided here courtesy of American Society for Clinical Investigation

RESOURCES