Picomole doses of platelet-activating factor predispose the gastric mucosa to damage by topical irritants

Prostaglandins
J L Wallace, B J Whittle

Abstract

The ability of the endogenous pro-inflammatory phospholipid, platelet-activating factor (Paf), to increase the susceptibility of the rat gastric mucosa to damage induced by a topical irritant was studied in an ex vivo gastric chamber model. Intravenous infusion of Paf (1-100 ng/kg/min) for 5 minutes dose-dependently increased the haemorrhagic damage induced by topically applied 20% ethanol. The pro-ulcerogenic actions of Paf were not solely due to its hypotensive actions, since a significant augmentation of damage was observed with doses of Paf (1 ng/kg/min) which did not affect systemic arterial blood pressure. These pro-ulcerogenic actions were not shared by the structurally similar precursor/breakdown product, lyso-Paf (100 ng/kg/min). Paf (100 ng/kg/min) also significantly increased the gastric damage induced by topically applied 2 mM sodium taurocholate. Infusion of Paf for 5 minutes without topical irritation only caused significant gastric damage at the highest dose tested (100 ng/kg/min). Histologically, this damage was characterized by extensive vasocongestion, deep mucosal necrosis, swelling of the gastric glands and accumulations of neutrophils in the mucosal and submucosal venules. Paf is thus a potent pro-ulcerogen...Continue Reading

References

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Citations

Feb 1, 1988·Digestive Diseases and Sciences·J L Wallace, B J Whittle
May 1, 1989·Digestive Diseases and Sciences·R A KozolS A Elgebaly
Jan 1, 1992·Agents and Actions·N K Boughton-SmithB J Whittle
Jun 22, 1988·European Journal of Pharmacology·J L Wallace, W K MacNaughton
May 19, 1989·European Journal of Pharmacology·S J KonturekG Beck
Dec 1, 1990·British Journal of Pharmacology·I R HutchesonN K Boughton-Smith
Jan 1, 1992·Annals of the New York Academy of Sciences·B J WhittleS Moncada
Jan 1, 1995·Mediators of Inflammation·A P DijkF J Zijlstra
Jun 1, 1994·The Journal of Clinical Investigation·G AmbrosioM Triggiani
Feb 1, 1987·Pharmacological Research Communications·A BrambillaA Giachetti
Nov 1, 1991·Prostaglandins, Leukotrienes, and Essential Fatty Acids·J SugataniK Saito
Jan 1, 1991·Scandinavian Journal of Gastroenterology. Supplement·J L Wallace
Sep 1, 1990·Scandinavian Journal of Gastroenterology·Z AckermanD Rachmilewitz
Dec 18, 2001·Experimental Biology and Medicine·J L Wallace, L Ma
Jan 1, 1988·British Journal of Pharmacology·J V Esplugues, B J Whittle
Mar 1, 1996·Infection and Immunity·E IsogaiH Isogai

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