Morphine dose-dependently (0.6, 1, and 5 μM) potentiated platelet aggregation and ATP release stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Furthermore, morphine (1 and 5 μM) markedly potentiated collagen (1 μg/ml) evoked an increase of intracellular Ca2+ mobilization in fura 2-AM loading human platelets. Morphine (1 and 5 μM) did not influence the binding of fluorescein isothiocyanate-triflavin to platelet glycoprotein IIb/IIIa complex. Yohimbine (0.1 μM), a specific α2-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by collagen. Moreover, morphine (0.6-5 μM) markedly inhibited prostaglandin E1 (10 μM)-induced cAMP formation in human platelets, and yohimbine (0.1 μM) significantly reversed the inhibition of cAMP by morphine (0.6 and 1 μM) in this study. Morphine (1 and 5 μM) 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 μM) did not significantly affect nitrate production in human platelets. Morphine may exert its potentiation in platelet aggregation by binding to α2-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 A2 formation and finally potentiates platelet aggregation and ATP release.
- Platelet aggregation
- Thromboxane A
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine