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The effect of inhibitors of platelet aggregation on the metabolism of platelet‐activating factor (PAF) in washed rabbit platelets
Author(s) -
O'Neill C.,
Ammit A. J.,
Korth R.,
Fleming S.,
Wells X.
Publication year - 1991
Publication title -
lipids
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.601
H-Index - 120
eISSN - 1558-9307
pISSN - 0024-4201
DOI - 10.1007/bf02536493
Subject(s) - platelet , platelet activating factor , clinical chemistry , chemistry , rabbit (cipher) , lipidology , platelet aggregation , pharmacology , biochemistry , medicine , statistics , mathematics
The rabbit platelet metabolizes platelet‐activating factor (PAF) intracellulary. PAF is deacetylated to produce lysoPAF which, in turn, can be acylated to produce 1‐ O ‐alkyl‐2‐acyl‐ sn ‐glycero‐3‐phosphocholine (alkylacyl GPC). Some PAF receptor antagonists have been shown to inhibit this metabolic conversion. In the present study we examined whether the PAF receptor antagonists SRI 63‐441 and WEB 2086 would inhibit the metabolism of PAF by intact rabbit platelets. In addition, we examined whether iloprost, a stable analogue of prostaglandin I 2 (PGI 2 ), and a potent inhibitor of platelet activation induced by a range of agonists, would also inhibit PAF metabolism. We found that SRI 63‐441 and WEB 2086 caused an almost complete inhibition of the conversion of PAF to alkylacyl GPC. Iloprost caused up to a 50% inhibition of PAF metabolism compared to antagonist‐free controls. Iloprost (and PGI 2 ) is thought to inhibit platelet response by elevation of cAMP, while receptor antagonists act by blocking PAF binding to its receptor. Since iloprost caused partial inhibition of PAF metabolism, the results of this study suggest that inhibition of PAF metabolism does not occur solely due to competitive inhibition of PAF binding to its receptor.