- 作者: George Hsiao Ming-Yi Shen Chiao-Ling Fang Duen-Suey Chou Chien-Huang LIn Tzeng-Fu Chen Joen-Rong Sheu
- 作者服務機構: Department of Pharmacology and GraduateInstitute of Medical Sciences, Taipei Medical University, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: The detailed mechanisms underlying morphine-signal-ing pathways in platelets remain obscure. Therefore, wesystematically examined the influence of morphine onwashed human platelets. In this study, washed humanplatelet suspensions were used for in vitro studies. Fur-thermore, platelet thrombus formation induced by irra-diation of mesenteric venules with filtered light in micepretreated with fluorescein sodium was used for an invivo thrombotic study. Morphine concentration depen-dently (0.6, 1, and 5μM) potentiated platelet aggregationand the ATP release reaction stimulated by agonists (i.e.,collagen and U46619) in washed human platelets. Yo-himbine (0.1μM), a specific α -adrenoceptor antagonist,markedly abolished the potentiation of morphine inplatelet aggregation stimulated by agonists. Morphinealso potentiated phosphoinositide breakdown and intra-cellular Ca mobilization in human platelets stimulatedby collagen (1μg/ml). Moreover, morphine (0.6-5μM)markedly inhibited prostaglandin E (10μM)-induced cy-clic AMP formation in human platelets, while yohimbine(0.1μM) significantly reversed the inhibition of cyclicAMP by morphine (0.6 and 1μM) in this study. Thethrombin-evoked increase in pH; was markedly poten-tiated in the presence of morphine (1 and 5μM). Mor-phine (2 and 5 mg/g) significantly shortened the timerequire to induce platelet plug formation in mesentericvenules. We concluded that morphine may exert itspotentiation in platelet aggregation by binding to α -adrenoceptors in human platelets, with a resulting inhi-bition of adenylate cyclase, thereby reducing intracellu-lar cyclic AMP formation followed by increased activa-tion of phospholipase C and the Na /H exchanger. Thisleads to increased intracellular Ca mobilization, andfinally potentiation of platelet aggregation and of theATP release reaction.
- 中文關鍵字: --
- 英文關鍵字: Morphine. Thrombosis. Adrenoceptors. cyclic AMP. Na/H exchanger