Influence of Cytoplasmic pH on the Aggregation and Ca^<2+> Mobilization in Rabbit Platelets
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概要
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The aggregability of rabbit platelets was studied under various cytoplasmic pHs (pH_i). Nigericin, a K^+/H^+ ionophore, which can induce a decrease in pH_i, at 2-10 μM in 2 min incubation reduced both platelet aggregation and an increase in cytoplasmic free Ca^<2+> concentration ([Ca^<2+>]_i) stimulated with thrombin or U46619. The reduced aggregability recovered 10 min after incubation with nigericin in parallel with an increase in pH_i. In contrast, when pH_i was increased by simultaneous addition of NH_4Cl, methylamine or monensin, aggregation in response to a low concentration of thrombin, U46619,arachidonic acid or A23187 was enhanced significantly. The enhancing effect of NH_4Cl was lowered by prolonged incubation with NH_4Cl, by which the increased pH_i was improved concomitantly. Indomethacin, an inhibitor of cyclooxygenase, failed to inhibit the enhancement of aggregation by NH_4Cl under stimulation with U46619. In addition, treatment with NH_4Cl enhanced an increase in [Ca^<2+>]_i in response to U46619 in a concentration-dependent manner, although the treatment by NH_4Cl alone did not affect [Ca^<2+>]_i. When pH_i was artificially altered during the ranges of 6.6-7.4 by treatment with nigericin in K^+-rich medium, aggregation by low concentration of thrombin was dependent on the pH_i. These data indicate that pH _i is an important factor for platelet activation including intracellular Ca^<2+> mobilization and aggregation.
- 公益社団法人日本薬学会の論文
- 1999-07-15
著者
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SATO Takashi
Department of Neurosurgery, University of Yamanashi, Faculty of Medicine
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HASHIZUME Tsutomu
Department of Pathological Biochemistry, Kyoto Pharmaceutical University
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Hashizume Tsutomu
Department Of Pathological Biochemistry Kyoto Pharmaceutical University
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Sato Takashi
Department Of Communications And Computer Engineering Kyoto University
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Sato Takashi
Department Of Applied Biochemistry And Food Science Saga University
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