Skip to main content
PMC home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1975 Feb;53(2):217–224. doi: 10.1111/j.1476-5381.1975.tb07351.x

Investigation of the vasodilator and antisecretory role of prostaglandins in the rat gastric mucosa by use of non-steroidal anti-inflammatory drugs.

I H Main, B J Whittle
PMCID: PMC1666300  PMID: 167892

Abstract

1 The effects of non-steroidal anti-inflammatory drugs on gastric acid secretion and mucosal blood flow were studied in the rat. 2 Indomethacin, in ulcerogenic doses, caused a dose-dependent rise in pentagastrin-stimulated acid secretion, but decreased mucosal blood flow per unit acid secretion. 3 During resting conditions, indomethacin had no significant effect on acid output, but reduced mucosal blood flow. 4 Pretreatment with indomethacin, phenylbutazone or meclofenamate potentiated the secretory response to dibutyryl cyclic adenosine 3',5'-monophosphate. 5 Indomethacin markedly reduced the mucosal prostaglandin-like activity at a time when mucosal erosion formation had reached steady levels. 6 These results provide evidence that prostaglandins have a local role in the regulation of blood flow and acid secretion in the rat gastric mucosa, and suggest that non-steroidal anti-inflammatory drugs cause mucosal erosions by disrupting these processes.

Full text

PDF
217

Selected References

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

  1. Alp M. H., Hislop I. G., Grant A. K. Gastric ulcer in South Australia 1954-1963. I. Epidemiological factors. Med J Aust. 1970 Dec 12;2(24):1128–1132. doi: 10.5694/j.1326-5377.1970.tb63388.x. [DOI] [PubMed] [Google Scholar]
  2. Augur N. A., Jr Gastric mucosal blood flow following damage by ethanol, acetic acid, or aspirin. Gastroenterology. 1970 Mar;58(3):311–320. [PubMed] [Google Scholar]
  3. Bennett A., Stamford I. F., Unger W. G. Prostaglandin E2 and gastric acid secretion in man. J Physiol. 1973 Mar;229(2):349–360. doi: 10.1113/jphysiol.1973.sp010142. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Cehovic G., Posternak T., Charollais E. A study of the bioloical activity and resistance to phosphodiesterase of some derivatives and analogues of cyclic AMP. Adv Cyclic Nucleotide Res. 1972;1:521–540. [PubMed] [Google Scholar]
  5. Chvasta T. E., Cooke A. R. The effect of several ulcerogenic drugs on the canine gastric mucosal barrier. J Lab Clin Med. 1972 Feb;79(2):302–315. [PubMed] [Google Scholar]
  6. DAVENPORT H. W. GASTRIC MUCOSAL INJURY BY FATTY AND ACETYLSALICYLIC ACIDS. Gastroenterology. 1964 Mar;46:245–253. [PubMed] [Google Scholar]
  7. Dozois R. R., Thompson C. J. Proceedings: Release of prostaglandins in canine gastric secretions in response to graded pentagastrin stimulation. Br J Pharmacol. 1974 Sep;52(1):151P–151P. [PMC free article] [PubMed] [Google Scholar]
  8. Flores A. G., Sharp G. W. Endogenous prostaglandins and osmotic water flow in the toad bladder. Am J Physiol. 1972 Dec;223(6):1392–1397. doi: 10.1152/ajplegacy.1972.223.6.1392. [DOI] [PubMed] [Google Scholar]
  9. Flower R. J., Vane J. R. Inhibition of prostaglandin synthetase in brain explains the anti-pyretic activity of paracetamol (4-acetamidophenol). Nature. 1972 Dec 15;240(5381):410–411. doi: 10.1038/240410a0. [DOI] [PubMed] [Google Scholar]
  10. GREEN K., SAMUELSSON B. PROSTAGLANDINS AND RELATED FACTORS: XIX. THIN-LAYER CHROMATOGRAPHY OF PROSTAGLANDINS. J Lipid Res. 1964 Jan;5:117–120. [PubMed] [Google Scholar]
  11. Horton E. W., Main I. H. Identification of prostaglandins in central nervous tissues of the cat and chicken. Br J Pharmacol Chemother. 1967 Aug;30(3):582–602. doi: 10.1111/j.1476-5381.1967.tb02165.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Horton E. W., Main I. H., Thompson C. J., Wright P. M. Effect of orally administered prostaglandin E1 on gastric secretion and gastrointestinal motility in man. Gut. 1968 Dec;9(6):655–658. doi: 10.1136/gut.9.6.655. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Johnson L. R. Histamine liberation by gastric mucosa of pylorus-ligated rats damaged by acetic or salicylic acids. Proc Soc Exp Biol Med. 1966 Feb;121(2):384–386. doi: 10.3181/00379727-121-30784. [DOI] [PubMed] [Google Scholar]
  14. Lee Y. H., Mollison K. W., Cheng W. D. The effects of anti-ulcer agents on indomethacin-induced gastric ulceration in the rat. Arch Int Pharmacodyn Ther. 1971 Aug;192(2):370–377. [PubMed] [Google Scholar]
  15. Main I. H., Whittle B. J. Effects of indomethacin on rat gastric acid secretion and mucosal blood flow. Br J Pharmacol. 1973 Mar;47(3):666P–666P. [PMC free article] [PubMed] [Google Scholar]
  16. Main I. H., Whittle B. J. Proceedings: Potentiation of dubutyryl cyclic 3'5'-AMP-induced gastric acid secretion in rats by non-steroidal anti-inflammatory drugs. Br J Pharmacol. 1973 Sep;49(1):162P–163P. [PMC free article] [PubMed] [Google Scholar]
  17. 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]
  18. Main I. H., Whittle B. J. The effects E and A prostaglandins on gastric mucosal blood flow and acid secretion in the rat. Br J Pharmacol. 1973 Nov;49(3):428–436. doi: 10.1111/j.1476-5381.1973.tb17253.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Mangla J. C., Kim Y. M., Rubulis A. A. Adenyl cyclase stimulation by aspirin in rat gastric mucosa. Nature. 1974 Jul 5;250(461):61–62. doi: 10.1038/250061a0. [DOI] [PubMed] [Google Scholar]
  20. Newcombe D. S., Thanassi N. M., Ciosek C. P., Jr Cartilage cyclic nucleotide phosphodiesterase: inhibition by anti-inflammatory agents. Life Sci. 1974 Feb 1;14(3):505–519. doi: 10.1016/0024-3205(74)90365-8. [DOI] [PubMed] [Google Scholar]
  21. Nicoloff D. M. Indomethacin. Effect on gastric secretion, parietal cell population, and ulcer provocation in the dog. Arch Surg. 1968 Nov;97(5):809–815. doi: 10.1001/archsurg.1968.01340050149024. [DOI] [PubMed] [Google Scholar]
  22. O'Brien P., Silen W. Effect of bile salts and aspirin on the gastric mucosal blood flow. Gastroenterology. 1973 Feb;64(2):246–253. [PubMed] [Google Scholar]
  23. Vane J. R. Inhibition of prostaglandin synthesis as a mechanism of action for aspirin-like drugs. Nat New Biol. 1971 Jun 23;231(25):232–235. doi: 10.1038/newbio231232a0. [DOI] [PubMed] [Google Scholar]
  24. 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]
  25. Wilhelmi G. Species differences in susceptibility to the gastro-ulcerogenic action of anti-inflammatory agents. Pharmacology. 1974;11(4):220–230. doi: 10.1159/000136493. [DOI] [PubMed] [Google Scholar]
  26. Winship D. H., Bernhard G. C. Basal and histamine-stimulated human gastric acid secretion. Lack of effect of indomethacin in therapeutic doses. Gastroenterology. 1970 Jun;58(6):762–765. [PubMed] [Google Scholar]

Articles from British Journal of Pharmacology are provided here courtesy of The British Pharmacological Society

RESOURCES