Vasoconstrictor expression of human platelet-vessel wall interactions: inhibition by the Ca2+ entry blocker flunarizine.
Human blood platelets, stimulated with thrombin, induced contractions of isolated basilar artery segments of the dog. These platelet-mediated vascular contractions were inhibited in a concentration-dependent way by flunarizine, a Ca2+ entry blocker, selective for vascular tissues (IC50: 5.5 X 10(-7) M). This inhibition increased gradually as a function of the time contact with flunarizine, to reach its maximum after 60-90 min. Biochemical and pharmacological analyses using the S2-serotonin receptor antagonist ritanserin, the thromboxane A2/prostaglandin endoperoxide antagonist BM 13.177 and the fatty acid cyclo-oxygenase inhibitor suprofen showed that 5-hydroxytryptamine and prostanoids (thromboxane A2, prostaglandin endoperoxides) were the main mediators involved. The results further suggested amplification between the vascular effects of 5-hydroxytryptamine and prostanoids. Flunarizine did not affect the release of 5-hydroxytryptamine from platelets and did not interfere with their biosynthesis of thromboxane A2.
D000818:Animals; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism; D001488:Basilar Artery / Q000187:drug effects*; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D004285:Dogs; D005444:Flunarizine / Q000494:pharmacology*; D066298:In Vitro Techniques; D010880:Piperidines / Q000494:pharmacology; D016713:Ritanserin; D012701:Serotonin / Q000378:metabolism; D013928:Thromboxane A2 / Q000096:biosynthesis; D014665:Vasodilator Agents
D001095:Arachidonic Acids; D010880:Piperidines; D014665:Vasodilator Agents; D016713:Ritanserin; D016718:Arachidonic Acid; D012701:Serotonin; D013928:Thromboxane A2; D005444:Flunarizine