NQ-Y15 inhibits the calcium mobilization by elevation of cyclic AMP in ratplatelets

2-[(4-Cyanophenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15) is a dual a ction drug which acts as a thromboxane A(2) (TXA(2)) synthase inhibitor and TXA(2)/PGH(2) receptor antagonist. In the present study, we examined the e ffects of NQ-Y15 on Ca2+ mobilization, which is the common event in various types of platelet activation, in arachidonic acid (AA)-stimulated rat plat elets. The elevation of cytosolic Ca2+ concentration ([Ca2+](i)) induced by AA was inhibited by NQ-Y15 in a concentration-dependent manner, This inhib ition-effect of NQ-Y15 was found to be based on the suppression of the rise in [Ca2+](i) by the inhibition of both Ca2+ release from internal stores a nd Ca2+ influx from the extracellular space. Our successive trial was focus ed on the role of cyclic AMP (cAMP) in the action of NQ-Y15, because cAMP w as reported to be increased by dual action drugs such as picotamide and to inhibit the increase in [Ca2+](i). NQ-Y15 was confirmed to increase cAMP in AA-stimulated rat platelets. These results suggested that NQ-Y15 might inh ibit the rise in [Ca2+](i) in AA-treated rat platelets bit increasing cAMP, which is involved in the inhibition of platelet activation.