NQ-Y15 Inhibits the Calcium Mobilization by Elevation of Cyclic AMP in Rat Platelets

抄録

2-[(4-Cyanophenyl)amino]-3-chloro-1,4-naphthalenedione (NQ-Y15) is a dual action drug which acts as a thromboxane A₂ (TXA₂) synthase inhibitor and TXA₂/PGH₂ receptor antagonist. In the present study, we examined the effects of NQ-Y15 on Ca²⁺ mobilization, which is the common event in various types of platelet activation, in arachidonic acid (AA)-stimulated rat platelets. The elevation of cytosolic Ca²⁺ concentration ([Ca²⁺]_i) induced by AA was inhibited by NQ-Y15 in a concentration-dependent manner. This inhibition-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 and Ca²⁺ influx from the extracellular space. Our successive trial was focused on the role of cyclic AMP (cAMP) in the action of NQ-Y15, because cAMP was 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 inhibit the rise in [Ca²⁺]_i in AA-treated rat platelets by increasing cAMP, which is involved in the inhibition of platelet activation.