Effect of Orthovanadate on Platelet Aggregation Induced by Platelet-Activating Factor(Biochemistry/Molecular Biology)
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概要
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Orthovanadate (vanadate) inhibited the platelet aggregation induced by platelet-activating factor (PAF) in a dose-dependent manner. Propranolol, a nonspecific β-adrenergic receptor antagonist, and H-8, a selective inhibitor of cAMP-dependent protein kinase (PKA), suppressed the inhibition of the PAF-induced platelet aggregation by vanadate. Vanadate increased the cAMP content in platelets accompanied by the activation of PKA. The β-adrenergic receptors of platelets have been reported to be abundant in the β_2 isoform, coupled to adenylyl cyclases (R. Kerry and M. C. Scrutton, Br. J. Pharmacol, 79, 681-691 (1983)). When the washed platelets were preincubated with vanadate, salbutamol, a selective β_2-adrenergic receptor agonist, or 8-Br-cAMP, the latter two mimicked the vanadate-induced anti-platelet aggregation and prolongation of clotting time of plasma, suggesting involvement of the increased intracellular cAMP content in both actions of vanadate. Butoxamine, a selective β_2-adrenergic receptor antagonist, suppressed both actions of vanadate. The vanadate-induced increase in cAMP content was inhibited in part by butoxamine or genistein. These results suggest that vanadate inhibits the PAF-induced platelet aggregation by the stimulation of a cAMP/PKA-dependent process via the β_2-adrenergic receptor and receptor tyrosine kinases, and that the anti-platelet aggregation is involved in part in mechanisms of the anticoagulant action of vanadate.
- 公益社団法人日本薬学会の論文
- 2004-11-01
著者
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Ueki Hiroshi
Department Of Biochemistry Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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SUENAGA Aya
Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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Suenaga Aya
Department Of Biochemistry Faculty Of Pharmacy And Pharmaceutical Sciences Fukuyama University
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Suenaga (nee
Department of Biochemistry, Faculty of Pharmacy and Pharmaceutical Sciences, Fukuyama University
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