Phosphatidylinositol 3-kinase inhibitor, wortmannin, inhibits 5-hydroxytryptamine-mediated potentiation of platelet aggregation induced by epinephrine.
The role of phosphatidylinositol 3-kinase (PI 3-kinase) was investigated in human platelets exposed to varying doses of 5-hydroxytryptamine (5-HT) and subthreshold doses of epinephrine. The synergistic effect of 5-HT on epinephrine-induced aggregation was blocked by a specific inhibitor of PI 3-kinase, wortmannin, in a dose-dependent manner. However, there was no effect of inhibitors of protein kinase A (PKA) or protein kinase C (PKC). These studies suggest a role of PI 3-kinase in the 5-HT induced potentiation of epinephrine-mediated platelet aggregation.
Shah
B H
BH
Department of Pharmacology and Physiology, Aga Khan University, Karachi, Pakistan.
Saeed
S A
SA
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology*; D000730:Androstadienes / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D004837:Epinephrine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000037:antagonists & inhibitors* / Q000502:physiology; D010974:Platelet Aggregation / Q000187:drug effects*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors; D012701:Serotonin / Q000494:pharmacology*; D012702:Serotonin Antagonists / Q000494:pharmacology*; D000077191:Wortmannin
D000316:Adrenergic alpha-Agonists; D000730:Androstadienes; D004791:Enzyme Inhibitors; D012702:Serotonin Antagonists; D012701:Serotonin; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C; D000077191:Wortmannin; D004837:Epinephrine