13-Azaprostanoic acid: a specific antagonist of the human blood platelet thromboxane/endoperoxide receptor.
A newly synthesized 13-aza derivative of prostanoic acid (13-APA) specifically inhibited human platelet aggregation induced by arachidonic acid, prostaglandin H2, or the stable endoperoxide analog (15S)-hydroxy-9 alpha,11 alpha-)epoxymethano)-prosta-5Z,13E-dienoic acid. 13-APA also inhibited [14C]serotonin release in response to arachidonic acid, ADP, or thrombin, but did not inhibit primary aggregation induced by ADP or thrombin. 13-APA completely blocked prostaglandin H2-induced aggregation in indomethacin-treated resuspended platelets but did not inhibit thromboxane synthesis. We therefore conclude that 13-APA acts as a direct antagonist of the platelet thromboxane/endoperoxide receptor.
D000244:Adenosine Diphosphate / Q000037:antagonists & inhibitors / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000494:pharmacology*; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D011449:Prostaglandin Endoperoxides / Q000037:antagonists & inhibitors*; D011463:Prostaglandins H / Q000037:antagonists & inhibitors*; D011466:Prostanoic Acids / Q000494:pharmacology*; D011955:Receptors, Drug / Q000187:drug effects*; D012701:Serotonin / Q000378:metabolism; D013917:Thrombin / Q000378:metabolism; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors*; D013929:Thromboxane B2 / Q000096:biosynthesis; D013931:Thromboxanes / Q000037:antagonists & inhibitors*
D005227:Fatty Acids; D011449:Prostaglandin Endoperoxides; D011463:Prostaglandins H; D011466:Prostanoic Acids; D011955:Receptors, Drug; D013931:Thromboxanes; D012701:Serotonin; D013929:Thromboxane B2; D013928:Thromboxane A2; D000244:Adenosine Diphosphate; D013917:Thrombin