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

J L Wallace, B J Whittle


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


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Dec 1, 1985·British Journal of Pharmacology·J L Wallace, B J Whittle
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Feb 1, 1988·Digestive Diseases and Sciences·J L Wallace, B J Whittle
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Jan 1, 1992·Agents and Actions·N K Boughton-SmithB J Whittle
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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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