グリア細胞におけるCa^<2+>アンチポーターによる細胞内Ca^<2+>調節

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We have previously demonstrated that the Na+-Ca2+ exchange activity was stimulated by nitric oxide (NO)/cGMP and inhibited by ascorbic acid. The present paper demonstrates that the Na+-Ca2+ exchanger is involved in agonist-induced Ca2+ signalling in cultured rat astrocytes. Astrocytic intracellular Ca2+ concentration ([Ca2+]i) was increased by L-glutamate, noradrenaline (NA) and ATP, and the increases were all attenuated by the NO generator sodium nitroprusside (SNP). SNP also reduced ionomycin-induced increase in [Ca2+]i. NA-induced Ca2+ signal was also attenuated by S-nitroso-L-cysteine and 8-bromo-cGMP, while it was enhanced by 3, 4-dichlorobenzamil, an inhibitor of the Na+-Ca2+ exchanger. Treatment of astrocytes with antisense, not sense, deoxynucleotides to the sequence encoding the Na+-Ca2+ exchanger enhanced ionomycin-induced increase in [Ca2+]i and blocked the effects of SNP and 8-bromo-cGMP in reducing NA-induced Ca2+ signal. Furthermore, ionomycin-induced Ca2+ signal was enhanced by removal of extracellular Na+ and pretreatment with ascorbic acid. These findings indicate that the Na+-Ca2+ exchanger is a target for NO modulation of elevated [Ca2+]i and the exchanger plays a role in Ca2+ efflux when [Ca2+]i is raised above basal levels in astrocytes.
社団法人日本薬理学会の論文
1996-09-20