Sheu Joen-Rong, Yeh Geng-Chang, Fang Chiao-Ling, Lin Chien-Huang, Hsiao George
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan.
J Cardiovasc Pharmacol. 2002 Nov;40(5):743-50. doi: 10.1097/00005344-200211000-00012.
Morphine dose-dependently (0.6, 1, and 5 microM) potentiated platelet aggregation and ATP release stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Furthermore, morphine (1 and 5 microM) markedly potentiated collagen (1 microg/ml) evoked an increase of intracellular Ca2+ mobilization in fura 2-AM loading human platelets. Morphine (1 and 5 microM) did not influence the binding of fluorescein isothiocyanate-triflavin to platelet glycoprotein IIb/IIIa complex. Yohimbine (0.1 microM), a specific alpha2-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by collagen. Moreover, morphine (0.6-5 microM) markedly inhibited prostaglandin E1 (10 microM)-induced cAMP formation in human platelets, and yohimbine (0.1 microM) significantly reversed the inhibition of cAMP by morphine (0.6 and 1 microM) in this study. Morphine (1 and 5 microM) significantly potentiated thromboxane B2 formation stimulated by collagen in human platelets, and yohimbine also reversed this effect of morphine in this study. In addition, morphine (1 and 5 microM) did not significantly affect nitrate production in human platelets. Morphine may exert its potentiation in platelet aggregation by binding to alpha2-adrenoceptors in human platelets, which leads to reduced cAMP formation and subsequently to increased intracellular Ca2+ mobilization; this, in turn, is followed by increased thromboxane A formation and finally potentiates platelet aggregation and ATP release.
吗啡在0.6、1和5微摩尔浓度下呈剂量依赖性地增强了洗涤后的人血小板中由激动剂（即胶原和U46619）刺激的血小板聚集和ATP释放。此外，吗啡（1和5微摩尔）显著增强了胶原（1微克/毫升）诱导的用fura 2 - AM负载的人血小板中细胞内Ca2+动员的增加。吗啡（1和5微摩尔）不影响异硫氰酸荧光素 - 三黄素与血小板糖蛋白IIb/IIIa复合物的结合。育亨宾（0.1微摩尔），一种特异性α2 - 肾上腺素能受体拮抗剂，显著消除了吗啡对胶原刺激的血小板聚集中的增强作用。此外，在本研究中，吗啡（0.6 - 5微摩尔）显著抑制了前列腺素E1（10微摩尔）诱导的人血小板中cAMP的形成，而育亨宾（0.1微摩尔）显著逆转了吗啡（0.6和1微摩尔）对cAMP的抑制作用。吗啡（1和5微摩尔）显著增强了胶原刺激的人血小板中血栓素B2的形成，并且育亨宾在本研究中也逆转了吗啡的这种作用。此外，吗啡（1和5微摩尔）对人血小板中硝酸盐的产生没有显著影响。吗啡可能通过与人血小板中的α2 - 肾上腺素能受体结合来增强血小板聚集，这导致cAMP形成减少，随后细胞内Ca2+动员增加；反过来，这接着导致血栓素A形成增加，最终增强血小板聚集和ATP释放。
