title: The effect of halofenate--free acid on aggregation--the release reaction, coagulant activity, and lipid metabolism of human platelets.
abstract: Halofenate--free acid (HFA), the major metabolite of the hypolipidemic drug, halofenate, inhibited platelet aggregation induced by collagen and sodium arachidonate and blocked the second phase of aggregation caused by ADP, thrombin and epinephrine in human platelet-rich plasma. The aggregation of washed platelets by thrombin and collagen was also blocked. HFA also inhibited the release by thrombin and collagen of 5-hydroxytryptamine from dense granules of platelets and the release by thrombin of beta-glucuronidase from platelet alpha-granules. These inhibitory effects were concentration and time-dependent. HFA decreased platelet factor 3 activity by 31% and also inhibited the incorporation of 14C-acetate and U-14C-glucose into platelet lipids by 89% and 56% respectively. Thrombin-induced lipid peroxidation and prostaglandin formation was investigated by measuring the by-product malonyldialdehyde, and this was found to be inhibited by HFA. It is suggested that the effect of HFA on aggregation is attributable to inhibition of the release reaction which may in turn be a consequence of the effects of the drug on platelet lipid synthesis.
mesh_terms: D001241:Aspirin / Q000494:pharmacology; D001779:Blood Coagulation Factors / Q000378:metabolism*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005089:Exocytosis / Q000187:drug effects; D005966:Glucuronidase / Q000097:blood; D006016:Glycolates / Q000494:pharmacology*; D006218:Halofenate / Q000494:pharmacology*; D006801:Humans; D008055:Lipids / Q000097:blood*; D008297:Male; D008315:Malondialdehyde / Q000097:blood; D010974:Platelet Aggregation / Q000187:drug effects*; D010977:Platelet Factor 3 / Q000378:metabolism*; D012701:Serotonin / Q000097:blood
chemical_list: D001779:Blood Coagulation Factors; D006016:Glycolates; D008055:Lipids; D012701:Serotonin; D010977:Platelet Factor 3; D008315:Malondialdehyde; D005966:Glucuronidase; D006218:Halofenate; D001241:Aspirin