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Marumo, M; Suehiro, A; Kakishita, E; Groschner, K; Wakabayashi, I.
Extracellular pH affects platelet aggregation associated with modulation of store-operated Ca(2+) entry.
Thromb Res. 2001; 104(5):353-360 Doi: 10.1016/S0049-3848(01)00374-7
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Groschner Klaus
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Abstract:
The pH dependence of store-operated Ca(2+) influx (SOCI) into human platelets, as well as its physiological consequence, aggregation, was studied. In Ca(2+)-free medium, thapsigargin (1 microM) induced a small increase in intracellular free-Ca(2+) ([Ca(2+)](i)), which was not affected by changes in extracellular pH. The addition of Ca(2+) (0.5-3 mM) after Ca(2+) store depletion caused by thapsigargin resulted in concentration-dependent increases in [Ca(2+)](i) (SOCI), which were strongly inhibited by SKF-96365 (100 microM), an inhibitor of receptor-mediated Ca(2+) entry. SOCI was inhibited by acidosis (pH 6.9) and augmented by alkalosis (pH 7.9). The addition of Ca(2+) (0.5-3 mM) to platelets, which were kept in Ca(2+)-free medium, slightly but significantly increased [Ca(2+)](i). This Ca(2+) leak entry was also decreased and increased by extracellular acidosis (pH 6.9) and alkalosis (pH 7.9), respectively, but not affected by SKF-96365. Neither thapsigargin (1 microM) stimulation in Ca(2+)-free solution nor elevation of extracellular Ca(2+) alone was sufficient to induce platelet aggregation. In contrast, the addition of Ca(2+) (1 mM) to platelets activated by thapsigargin resulted in aggregation, which was markedly inhibited by SKF-96365 (100 microM). Platelet aggregation associated with SOCI was also inhibited by extracellular acidosis (pH 6.9) and augmented by extracellular alkalosis (pH 7.9). These results suggest that acidosis-induced inhibition, as well as alkalosis-induced promotion of platelet aggregation, involve pH effects on SOCI.
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Blood Platelets - physiology
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Humans -
Hydrogen-Ion Concentration -
Imidazoles - pharmacology
Ion Transport - drug effects
Platelet Aggregation - drug effects
Thapsigargin - pharmacology

Find related publications in this database (Keywords)
acidosis
alkalosis
Ca2+ store
thapsigargin
platelet aggregation
Ca2+ channels
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