Potentiating effects of clofibrate on prostaglandin-dependent and -independent pathways of human platelet activation: evidence for involvement of cyclic AMP.
Although clofibrate has been shown to inhibit platelet aggregation that is caused by thrombin, ADP and epinephrine, by blocking the release of arachidonic acid from platelet phospholipids [8], here we have demonstrated that clofibrate enhanced platelet aggregation by arachidonic acid and PLC and reversed the effects of PGE1 on platelet cAMP concentration and on PLC-induced secretion of [14C]-5HT in similar, concentration-dependent manners. Taken together, these findings strongly suggest that the proaggregatory effect of clofibrate is mediated by a lowering of cAMP in platelets.
D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001792:Blood Platelets / Q000187:drug effects*; D002994:Clofibrate / Q000494:pharmacology*; D000242:Cyclic AMP / Q000502:physiology*; D006801:Humans; D066298:In Vitro Techniques; D010101:Oxygen Consumption / Q000187:drug effects; D010974:Platelet Aggregation / Q000187:drug effects; D011453:Prostaglandins / Q000502:physiology*; D013997:Time Factors; D010738:Type C Phospholipases / Q000494:pharmacology
D001095:Arachidonic Acids; D011453:Prostaglandins; D016718:Arachidonic Acid; D000242:Cyclic AMP; D010738:Type C Phospholipases; D002994:Clofibrate