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

• Published in: Biological & pharmaceutical bulletin Vol. 24; no. 5; pp. 480 - 483
• Main Authors: CHANG, Tong-Shin, LEE, Ki-Seon, LEE, Gwi-Yeop, JEON, Sun-Duck, SO, Dhong-Su, KHIL, Lee-Yong, CHUNG, Myung-Kiu, MOON, Chang-Kiu
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.05.2001; Maruzen; Japan Science and Technology Agency
• Subjects: 2-[(4-cyanophenyl)amino]-3-chloro-1,4-naphthalenedione; Animals; Arachidonic Acid - pharmacology; Biological and medical sciences; Blood Platelets - drug effects; Blood Platelets - metabolism; Blood. Blood coagulation. Reticuloendothelial system; Calcium - metabolism; calcium mobilization; cyclic AMP; Cyclic AMP - biosynthesis; Enzyme Inhibitors - pharmacology; Female; Medical sciences; Naphthoquinones - pharmacology; Pharmacology. Drug treatments; platelet; Platelet Aggregation Inhibitors - pharmacology; Prostaglandin D2 - pharmacology; Rats; Rats, Sprague-Dawley; Receptors, Thromboxane - antagonists & inhibitors; Thromboxane-A Synthase - antagonists & inhibitors; Rat; Enzyme; Thromboxane A2; Rodentia; Prostaglandin H2; Cyclic AMP; Enzyme inhibitor; Synthase; Arachidonic acid; Naphthalene derivatives; Vertebrata; Platelet; Mammalia; Animal; Antagonist; Calcium Cations
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.24.480

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.