4,5-DIPHENYL-2-OXAZOLYL)-5-OXAZOLYL]PHENOXY]ACETIC ACID (BMY-45778) IS A POTENT NONPROSTANOID PROSTACYCLIN PARTIAL AGONIST - EFFECTS ON PLATELET-AGGREGATION, ADENYLYL-CYCLASE, CAMP LEVELS, PROTEIN-KINASE, AND ILOPROST BINDING

-(4,5-diphenyl-2-oxazolyl)-5-oxazol]phenoxy]acetic acid (BMY 45778) in hibits human (IC50 = 35 nM), rabbit (136 nM) and rat (1.3 mu M) platel et aggregation. This compound activates adenylyl cyclase (ED(50) = 6-1 0 nM) and stimulates GTPase in human platelet membrane preparations. T he potency (EC(50)) of BMY 45778 stimulating adenylyl cyclase is compa rable to iloprost. However, maximal stimulation of GTPase by BMY 45778 is approximately half the iloprost-stimulated activity, and BMY 45778 limits the GTPase stimulation by iloprost suggesting that BMY 45778 i s a partial agonist at the IP receptor. BMY 45778 completely prevents [H-3]]Iloprost binding to platelet membranes (IC50 = 7 nM). in whole p latelets, BMY 45778 causes elevation of platelet cAMP levels (cAMP con tent doubles at 13 nM) and activation of the cAMP-dependent protein ki nase (cAMP-protein kinase ratio is twice basal at 2 nM). BMY 45778 tre atment of whole platelets also desensitizes the adenylyl cyclase activ ation by iloprost. These results indicate that BMY 45778, which is str ucturally different from prostacyclin and most prostacyclin agonists, acts by stimulating prostacyclin (IF) receptors.