Salicylate reverses in vitro aspirin inhibition of rat platelet and vascular prostaglandin generation

Jaime Merino, Manuela Livio, Grazyna Rajtar, Giovanni de Gaetano

Research output: Contribution to journalArticle

Abstract

It is generally accepted that aspirin inhibits platelet function by irreversible acetylation of prostaglandin cyclo-oxygenase. The salicylate moiety seems not to be causally involved in the inhibitory effect of aspirin, a concept supported by the virtual inactivity of sodium salicylate. However, prostaglandin synthesis is also inhibited by numerous compounds which have no acetylating properties. Recent evidence indicates that salicylate may prevent the inhibitory effect of aspirin on rabbit platelet cyclo-oxygenase, suggesting that interaction of the salicylate moiety of aspirin with this enzyme is important. This study was aimed at evaluating whether the inhibitory effect of aspirin on platelet prostaglandin generation could be reversed by sodium salicylate. We therefore measured spectrophotometrically malondialdehyde (MDA) generated by arachidonate in rat platelet-rich plasma and evaluated the effect of short-term incubation with either aspirin or salicylate or both. In the experimental conditions used, salicylate not only prevented but also reversed aspirin-inhibition of MDA formation. This interaction was not peculiar for platelets, since salicylate also reversed the in vitro inhibitory effect of aspirin on vascular prostacyclin generation (measured by a bioassay). These findings suggest that irreversible acetylation of cyclo-oxygenase does not account for the early in vitro inhibitory effect of aspirin on prostaglandin synthesis.

Original languageEnglish
Pages (from-to)1093-1096
Number of pages4
JournalBiochemical Pharmacology
Volume29
Issue number8
DOIs
Publication statusPublished - Apr 15 1980

ASJC Scopus subject areas

  • Pharmacology

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