Abstract

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.

Original languageEnglish
Pages (from-to)743-750
Number of pages8
JournalJournal of Cardiovascular Pharmacology
Volume40
Issue number5
DOIs
Publication statusPublished - Nov 1 2002

Fingerprint

Platelet Aggregation
Adrenergic Receptors
Morphine
Blood Platelets
Yohimbine
Collagen
Adenosine Triphosphate
Integrin beta3
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Thromboxane B2
Platelet Glycoprotein GPIIb-IIIa Complex
Thromboxane A2
Fura-2
Alprostadil
Fluorescein
Nitrates

Keywords

  • Adrenoceptors
  • cAMP
  • Morphine
  • Platelet aggregation
  • Thromboxane A

ASJC Scopus subject areas

  • Pharmacology
  • Cardiology and Cardiovascular Medicine

Cite this

Morphine-potentiated agonist-induced platelet aggregation through α2-adrenoceptors in human platelets. / Sheu, Joen Rong; Yeh, Geng Chang; Fang, Chiao Ling; Lin, Chien-Huang; Hsiao, George.

In: Journal of Cardiovascular Pharmacology, Vol. 40, No. 5, 01.11.2002, p. 743-750.

Research output: Contribution to journalArticle

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AU - Lin, Chien-Huang

AU - Hsiao, George

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N2 - 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.

AB - 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.

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