Abstract

The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 μM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 μM), a specific α2-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca2+ mobilization in human platelets stimulated by collagen (1 μg/ml). Moreover, morphine (0.6-5 μM) markedly inhibited prostaglandin E1 (10 μM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 μM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 μM) in this study. The thrombin-evoked increase in pHi was markedly potentiated in the presence of morphine (1 and 5 μM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to α2-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na+/H+ exchanger. This leads to increased intracellular Ca2+ mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.

Original languageEnglish
Pages (from-to)292-301
Number of pages10
JournalJournal of Biomedical Science
Volume10
Issue number3
DOIs
Publication statusPublished - 2003

Fingerprint

Platelets
Platelet Aggregation
Morphine
Blood Platelets
Agglomeration
Experiments
Cyclic AMP
Yohimbine
Venules
Adrenergic Receptors
Collagen
Adenosine Triphosphate
In Vitro Techniques
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Sodium-Hydrogen Antiporter
Alprostadil
Type C Phospholipases
Phosphatidylinositols
Fluorescein
Adenylyl Cyclases

Keywords

  • α-Adrenoceptors
  • Cyclic AMP
  • Morphine
  • Na/H exchanger
  • Thrombosis

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments. / Hsiao, George; Shen, Ming Yi; Fang, Chiao Ling; Chou, Duen Suey; Lin, Chien Huang; Chen, Tzeng-Fu; Sheu, Joen Rong.

In: Journal of Biomedical Science, Vol. 10, No. 3, 2003, p. 292-301.

Research output: Contribution to journalArticle

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abstract = "The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 μM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 μM), a specific α2-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca2+ mobilization in human platelets stimulated by collagen (1 μg/ml). Moreover, morphine (0.6-5 μM) markedly inhibited prostaglandin E1 (10 μM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 μM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 μM) in this study. The thrombin-evoked increase in pHi was markedly potentiated in the presence of morphine (1 and 5 μM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to α2-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na+/H+ exchanger. This leads to increased intracellular Ca2+ mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.",
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T1 - Morphine-potentiated platelet aggregation in in vitro and platelet plug formation in in vivo experiments

AU - Hsiao, George

AU - Shen, Ming Yi

AU - Fang, Chiao Ling

AU - Chou, Duen Suey

AU - Lin, Chien Huang

AU - Chen, Tzeng-Fu

AU - Sheu, Joen Rong

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N2 - The detailed mechanisms underlying morphine-signaling pathways in platelets remain obscure. Therefore, we systematically examined the influence of morphine on washed human platelets. In this study, washed human platelet suspensions were used for in vitro studies. Furthermore, platelet thrombus formation induced by irradiation of mesenteric venules with filtered light in mice pretreated with fluorescein sodium was used for an in vivo thrombotic study. Morphine concentration dependently (0.6, 1, and 5 μM) potentiated platelet aggregation and the ATP release reaction stimulated by agonists (i.e., collagen and U46619) in washed human platelets. Yohimbine (0.1 μM), a specific α2-adrenoceptor antagonist, markedly abolished the potentiation of morphine in platelet aggregation stimulated by agonists. Morphine also potentiated phosphoinositide breakdown and intracellular Ca2+ mobilization in human platelets stimulated by collagen (1 μg/ml). Moreover, morphine (0.6-5 μM) markedly inhibited prostaglandin E1 (10 μM)-induced cyclic AMP formation in human platelets, while yohimbine (0.1 μM) significantly reversed the inhibition of cyclic AMP by morphine (0.6 and 1 μM) in this study. The thrombin-evoked increase in pHi was markedly potentiated in the presence of morphine (1 and 5 μM). Morphine (2 and 5 mg/g) significantly shortened the time require to induce platelet plug formation in mesenteric venules. We concluded that morphine may exert its potentiation in platelet aggregation by binding to α2-adrenoceptors in human platelets, with a resulting inhibition of adenylate cyclase, thereby reducing intracellular cyclic AMP formation followed by increased activation of phospholipase C and the Na+/H+ exchanger. This leads to increased intracellular Ca2+ mobilization, and finally potentiation of platelet aggregation and of the ATP release reaction.

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