Modification of human platelet response to sodium arachidonate by membrane modulation.
Previous studies have shown that the majority of mongrel dogs have platelets that do not aggregate when stirred with sodium arachidonate, but respond normally to other aggregating agents. Here we have created a model in which human platelets mimic the unusual behavior of canine cells. Brief exposure of human platelets to low concentrations of prostacyclin will convert them to a physiologic state resembling that of canine platelets without causing elevation of intracellular levels of cAMP. Studies on the conversion of arachidonic acid showed that prostacyclin did not cause any inhibition of thromboxane B2 generation. Exposure of prostacyclin treated platelets to epinephrine restored their sensitivity to arachidonate without causing any detectable changes in levels of cAMP. The selective inhibition achieved by PGI2 could be mimicked by the endoperoxide analog. U44069, a thromboxane inhibitor, U-51605, and an endoperoxide/thromboxane receptor blocker, 13-APA. Inhibition induced by these compounds was also reversed by epinephrine. A calcium channel blocker, verapamil, and an alpha blocker, dihydroergocryptine, effectively blocked the corrective influence of epinephrine on prostacyclin-treated platelets. Results of these studies show that catecholamines and prostaglandin receptors share close sites on the membrane and exhibit a degree of cooperativity in calcium modulation. Dog platelets that do not respond to products of AA metabolism and the human platelets made to behave like canine platelets may have a defect in calcium mobilization and this defect is corrected by adrenaline through an alpha receptor modulation.
D000328:Adult; D001095:Arachidonic Acids / Q000378:metabolism / Q000494:pharmacology*; D001792:Blood Platelets / Q000378:metabolism; D002462:Cell Membrane / Q000378:metabolism; D000242:Cyclic AMP / Q000378:metabolism; D004088:Dihydroergotoxine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000494:pharmacology; D006801:Humans; D010974:Platelet Aggregation / Q000187:drug effects*; D013929:Thromboxane B2 / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D001095:Arachidonic Acids; D004088:Dihydroergotoxine; D013929:Thromboxane B2; D014700:Verapamil; D011464:Epoprostenol; D000242:Cyclic AMP; D004837:Epinephrine