Pharmacological interaction between serotonin<sub>2</sub> and α<sub>2</sub>-adrenergic receptors in the human platelet aggregation

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  • OKADA Hidetoshi
    Department of Clinical Neurochemistry, Institute for Neurobiology, Okayama University Medical School

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  • ヒト血小板凝集能におけるセロトニン<sub>2</sub>およびアルファ<sub>2</sub>-アドレナージック受容体の薬理学的相互作用
  • Pharmacological interaction between serotonin<sub>2</sub> and &alpha;<sub>2</sub>-adrenergic receptors in the human platelet aggregation

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To investigate the interaction between serotonin (5HT)2 and α2-adrenergic receptors in the human platelet membrane, the inhibitory effects of calcium (Ca) antagonists, 5HT2 antagonists, α2 antagonists and adenosine (AE) receptor (A2) agonists on 5HT plus ADP ([5HT+ADP]) and adrenaline (ADR) plus ADP ([ADR+ADP])-induced washed platelet aggregation were examined. In the [5HT+ADP] -induced aggregation. The inhibitory activity was in the order of (-)-desmethoxyverapamil (D888), mianserin (MA), ketanserin, AE>diltiazem, nicardipine, yohimbine. On the other hand, in the [ADR+ADP] -induced aggregation, the inhibitory activity was in the order of MA, YH>D888, AE, and the rest had no significant effect even at 10 μM. Only AE among these drugs inhibited ADP-induced aggregation. The present findings indicate that the Ca antagonist D888, 5HT2 antagonist MA and α2 antagonist YH acted simultaneously as 5HT2 and α2 receptor inhibitors and imply an apparent interaction between these receptors. Since both of the aggregation responses required extracellular Ca2+ and were modulated by Ca2+ concentrations, the mechanism of interaction may be attributed to intracellular Ca2+-signaling systems.

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