Nitroprusside and Cyclic GMP Stimulate Na+-Ca2+ Exchange Activity in Neuronal Preparations and Cultured Rat Astrocytes |
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Authors: | Shoichi Asano Toshio Matsuda Kazuhiro Takuma Hye Sun Kim Tomoaki Sato Takashige Nishikawa Akemichi Baba |
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Affiliation: | Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Osaka, and; Department of Pharmacology, Kagoshima University Dental School, Kagoshima Japan |
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Abstract: | Abstract: The effects of nitric oxide (NO)-generating agents on 45Ca2+ uptake in rat brain slices and cultured rat astrocytes were studied in the presence of monensin, which is considered to drive the Na+-Ca2+ exchanger in the reverse mode. Sodium nitroprusside (SNP) at >10 µ M increased monensin-stimulated Ca2+ uptake in the slices, although it did not affect high K+-stimulated Ca2+ uptake. Another NO donor, 3-morpholinosydnonimine, was effective. The effect of SNP was antagonized by hemoglobin (50 µ M ), a NO scavenger, and mimicked by 8-bromo-cyclic GMP (100 µ M ). In rat brain synaptosomes, SNP increased monensin-stimulated Ca2+ uptake, but it did not affect high K+-stimulated Ca2+ uptake. 8-Bromocyclic GMP, but not SNP, increased Na+-dependent Ca2+ uptake significantly in synaptic membrane vesicles in the absence of monensin. In cultured rat astrocytes, SNP and 8-bromo-cyclic GMP increased Ca2+ uptake in the presence of ouabain and monensin, which were required for the Ca2+ uptake in the cells. These findings suggest that NO stimulates the Na+-Ca2+ exchanger in neuronal preparations and astrocytes in a cyclic GMP-dependent mechanism. |
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Keywords: | Na+-Ca2+ exchanger Nitric oxide Cyclic GMP Brain slices Astrocytes Monensin |
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