Involvement of platelet-derived 5-hydroxytryptamine in thromboxane A2-induced aggregation in cat platelets.
The present study was undertaken to examine the involvement of platelet-derived serotonin (5-hydroxytryptamine; 5-HT) in thromboxane A2 (TXA2)-induced platelet aggregation. Pharmacological experiments with 5-HT2 and TXA2 inhibitors were conducted on platelet aggregation in platelet-rich plasma from cats. Exogenously added 5-HT, U-46619 (a stable TXA2 analogue) and collagen caused platelet aggregation in a concentration-dependent manner. The combination of low concentrations of 5-HT and U-46619 caused full platelet aggregation, whereas each agent alone, at these concentrations, caused a transient aggregation. 5-HT-induced aggregation was inhibited by ketanserin (0.01-0.3 micromol/l), a 5-HT2 receptor antagonist, in a concentration-dependent manner. Collagen-induced platelet aggregation was also inhibited by ketanserin, whereas the inhibition by indomethacin was modest even at the highest concentration tested (300 micromol/l). U-46619 triggered platelet aggregation in a biphasic manner. Ketanserin inhibited only the second phase of the aggregation. The inhibition of U-46619-induced aggregation by ketanserin occurred at a concentration range similar to that for 5-HT-induced platelet aggregation. Likewise, platelet aggregation induced by the combination of low concentrations of 5-HT and U-46619 was fully inhibited by ketanserin. These data suggest a major involvement of platelet-derived 5-HT in TXA2-dependent aggregation in cat platelets.
Ogawa
T
T
Pharmacology and Molecular Biology Research Laboratories, Sankyo Co. Ltd., Tokyo, Japan. togawa@shina.sankyo.co.jp
Sugidachi
A
A
Asai
F
F
Koike
H
H
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000818:Animals; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism*; D002415:Cats; D003094:Collagen / Q000494:pharmacology; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004347:Drug Interactions; D005260:Female; D007213:Indomethacin / Q000494:pharmacology; D007650:Ketanserin / Q000494:pharmacology; D008297:Male; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D012701:Serotonin / Q000494:pharmacology / Q000502:physiology*; D012702:Serotonin Antagonists / Q000494:pharmacology; D013449:Sulfonamides / Q000494:pharmacology; D013928:Thromboxane A2 / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D016861:Cyclooxygenase Inhibitors; D010975:Platelet Aggregation Inhibitors; D012702:Serotonin Antagonists; D013449:Sulfonamides; D012701:Serotonin; D013928:Thromboxane A2; C040624:sulotroban; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D003094:Collagen; D007650:Ketanserin; D007213:Indomethacin