Skip to main content
NCBI home page
British Journal of Pharmacology logoLink to British Journal of Pharmacology
. 1987 Feb;90(2):365–371. doi: 10.1111/j.1476-5381.1987.tb08966.x

Failure of prostaglandin E2 and its 16,16-dimethyl analogue to prevent the gastric mucosal damage induced by Paf.

G Steel, J L Wallace, B J Whittle
PMCID: PMC1916945  PMID: 3470106

Abstract

Intravenous and orally administered prostaglandin E2 (PGE2) and 16,16-dimethyl PGE2 (dmPGE2) protect the rat gastric mucosa from injury induced by oral administration of acidified 40% ethanol. The effects of pretreatment with these prostaglandins on platelet activating factor (Paf)-induced gastric damage has now been investigated in the rat. A 10 min infusion of Paf (50 or 100 ng kg-1 min-1, i.v.) resulted in dose-related vasocongestion of the gastric mucosa. Intravenous pretreatment with dmPGE2 (20 micrograms kg-1) failed to prevent the gastric damage induced by the higher dose of Paf. Pretreatment with PGE2 (10-100 micrograms kg-1) or dmPGE2 (1-20 micrograms kg-1), either orally or intravenously, also failed to prevent the gastric vasocongestion induced by the lower dose of Paf. On the contrary, significant augmentation of Paf-induced damage was observed with several of the doses of PGE2 and dmPGE2. These studies demonstrate that the protective properties of PGE2 and dmPGE2 in the gastric mucosa do not extend to damage induced by Paf.

Full text

PDF
365

Selected References

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

  1. Camussi G., Tetta C., Bussolino F. Inhibitory effect of prostacyclin (PGI2) on neutropenia induced by intravenous injection of platelet-activating-factor (PAF) in the rabbit. Prostaglandins. 1983 Mar;25(3):343–351. doi: 10.1016/0090-6980(83)90037-0. [DOI] [PubMed] [Google Scholar]
  2. Hawkey C. J., Rampton D. S. Prostaglandins and the gastrointestinal mucosa: are they important in its function, disease, or treatment? Gastroenterology. 1985 Nov;89(5):1162–1188. doi: 10.1016/0016-5085(85)90225-2. [DOI] [PubMed] [Google Scholar]
  3. Hsueh W., Gonzalez-Crussi F., Arroyave J. L. Platelet-activating factor-induced ischemic bowel necrosis. An investigation of secondary mediators in its pathogenesis. Am J Pathol. 1986 Feb;122(2):231–239. [PMC free article] [PubMed] [Google Scholar]
  4. Lacy E. R., Ito S. Microscopic analysis of ethanol damage to rat gastric mucosa after treatment with a prostaglandin. Gastroenterology. 1982 Sep;83(3):619–625. [PubMed] [Google Scholar]
  5. Main I. H., Whittle B. J. Potency and selectivity of methyl analogues of prostaglandin E2 on rat gastrointestinal function. Br J Pharmacol. 1975 Jul;54(3):309–317. doi: 10.1111/j.1476-5381.1975.tb07570.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. McGivern D. V., Basran G. S. Synergism between platelet-activating factor (PAF-acether) and prostaglandin E2 in man. Eur J Pharmacol. 1984 Jun 15;102(1):183–185. doi: 10.1016/0014-2999(84)90356-x. [DOI] [PubMed] [Google Scholar]
  7. Robert A., Nezamis J. E., Lancaster C., Hanchar A. J. Cytoprotection by prostaglandins in rats. Prevention of gastric necrosis produced by alcohol, HCl, NaOH, hypertonic NaCl, and thermal injury. Gastroenterology. 1979 Sep;77(3):433–443. [PubMed] [Google Scholar]
  8. Rosam A. C., Wallace J. L., Whittle B. J. Potent ulcerogenic actions of platelet-activating factor on the stomach. Nature. 1986 Jan 2;319(6048):54–56. doi: 10.1038/319054a0. [DOI] [PubMed] [Google Scholar]
  9. Wallace J. L., Morris G. P., Krausse E. J., Greaves S. E. Reduction by cytoprotective agents of ethanol-induced damage to the rat gastric mucosa: a correlated morphological and physiological study. Can J Physiol Pharmacol. 1982 Dec;60(12):1686–1699. doi: 10.1139/y82-247. [DOI] [PubMed] [Google Scholar]
  10. Wallace J. L., Whittle B. J. Effects of inhibitors of arachidonic acid metabolism on Paf-induced gastric mucosal necrosis and haemoconcentration. Br J Pharmacol. 1986 Oct;89(2):415–422. doi: 10.1111/j.1476-5381.1986.tb10275.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Wallace J. L., Whittle B. J. Picomole doses of platelet-activating factor predispose the gastric mucosa to damage by topical irritants. Prostaglandins. 1986 May;31(5):989–998. doi: 10.1016/0090-6980(86)90028-6. [DOI] [PubMed] [Google Scholar]
  12. Wallace J. L., Whittle B. J. Prevention of endotoxin-induced gastrointestinal damage by CV-3988, an antagonist of platelet-activating factor. Eur J Pharmacol. 1986 May 13;124(1-2):209–210. doi: 10.1016/0014-2999(86)90148-2. [DOI] [PubMed] [Google Scholar]
  13. Williams T. J., Peck M. J. Role of prostaglandin-mediated vasodilatation in inflammation. Nature. 1977 Dec 8;270(5637):530–532. doi: 10.1038/270530a0. [DOI] [PubMed] [Google Scholar]

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

RESOURCES