Morphine-potentiated agonist-induced platelet aggregation through alpha2-adrenoceptors in human platelets.
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.
Sheu
Joen-Rong
JR
Graduate Institute of Medical Sciences, Taipei Medical University, Taipei, Taiwan. sheujr@tmu.edu.tw
Yeh
Geng-Chang
GC
Fang
Chiao-Ling
CL
Lin
Chien-Huang
CH
Hsiao
George
G
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects* / Q000378:metabolism; D003094:Collagen / Q000494:pharmacology*; D000242:Cyclic AMP / Q000096:biosynthesis / Q000378:metabolism; D004357:Drug Synergism; D005434:Flow Cytometry; D006801:Humans; D009020:Morphine / Q000008:administration & dosage / Q000494:pharmacology*; D010455:Peptides / Q000494:pharmacology; D010974:Platelet Aggregation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D019039:Platelet Glycoprotein GPIIb-IIIa Complex / Q000187:drug effects / Q000494:pharmacology; D018341:Receptors, Adrenergic, alpha-2 / Q000187:drug effects* / Q000378:metabolism
D010455:Peptides; D010975:Platelet Aggregation Inhibitors; D019039:Platelet Glycoprotein GPIIb-IIIa Complex; D018341:Receptors, Adrenergic, alpha-2; C070025:triflavin; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D009020:Morphine; D003094:Collagen; D000242:Cyclic AMP