Augmentation of U46619 induced human platelet aggregation by aspirin.
Aspirin is known to suppress platelet function markedly. However, aspirin at concentrations higher than 1 mM was observed to augment 1.3 microM U46619 (a stable thromboxane receptor (TP receptor) agonist) induced human platelet aggregation in this study. Moreover, at a concentration as low as 250 microM aspirin increased the aggregation induced by U46619 in 13% of normal and healthy individuals. The degree of platelet aggregation and the amount of ATP release were enhanced in U46619 stimulated platelet rich plasma by the addition of aspirin (>250 microM). U46619 was previously reported to inhibit forskolin-stimulated adenyl cyclase and to reduce the cAMP formation. Both of the augmentation effects of aspirin on U46619-induced aggregation and ATP release were blocked by MeSAMP, a P2Y(12) receptor antagonist. U46619 induced aggregation was suppressed by the addition of ADP scavenger (CP/CPK) with no significant change on ATP measured and the effect of CP/CPK could not be reversed by aspirin. In addition, aspirin augmented the inhibitory effect of U46619 on the cAMP production. Our present results suggested that the potentiation effect of aspirin on U46619 induced aggregation was related with the secreted ADP and the subsequent P2Y(12)/Gi related signaling.
Kim
Jeong Mi
JM
Natural Products Research Institute, College of Pharmacy, Seoul National University, Seoul, Korea.
Koo
Yean Kyoung
YK
Jin
Jingling
J
Lee
Yong Yook
YY
Park
Seonyang
S
Yun-Choi
Hye Sook
HS
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology*; D000244:Adenosine Diphosphate / Q000378:metabolism; D000255:Adenosine Triphosphate / Q000378:metabolism; D000262:Adenylyl Cyclases / Q000378:metabolism; D000328:Adult; D001241:Aspirin / Q000494:pharmacology*; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology; D000242:Cyclic AMP / Q000378:metabolism; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D005260:Female; D006801:Humans; D008297:Male; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D015398:Signal Transduction / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D055815:Young Adult
D016861:Cyclooxygenase Inhibitors; C548576:P2RY12 protein, human; D010975:Platelet Aggregation Inhibitors; D058919:Purinergic P2 Receptor Antagonists; D058925:Receptors, Purinergic P2Y12; D014662:Vasoconstrictor Agents; D000244:Adenosine Diphosphate; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D000242:Cyclic AMP; D019001:Nitric Oxide Synthase; D000262:Adenylyl Cyclases; D001241:Aspirin