Potent ulcerogenic actions of platelet-activating factor on the stomach

Platelet-activating factor (PAF) is an endogenous phospholipid which has been implicated as a mediator of allergic and inflammatory processes. It is synthesized and released by neutrophils, platelets, macrophages, monocytes, basophils and endothelial cells, and is a potent platelet-aggregating agent, a vasodilator, increases vascular permeability, stimulates neutrophil aggregation and degranulation and induces release of lysosomal enzymes. A role for PAF in the hypotension associated with endotoxin shock and in necrotizing enterocolitis has recently been suggested. As there is an association between septic shock and acute gastric damage, we propose that PAF is an endogenous mediator of ulceration in the stomach. Indeed, as reported here, intravenous (i.v.) infusion of PAF to rats, at doses of 20-200 pmol per kg per min, resulted in the formation of extensive haemorrhagic erosions in the gastric mucosa. The ulcerogenic actions of PAF are not attributable solely to its hypotensive actions and were not mediated via effects on platelets or cyclooxygenase products, nor via histamine H1, H2 or alpha-adrenergic receptors. PAF is the most potent gastric ulcerogen yet described and its endogenous release may underlie or contribute to certain forms of gastric ulceration.