Nitroprusside and cyclic GMP stimulate Na(+)-Ca2+ exchange activity in neuronal preparations and cultured rat astrocytes.
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 microM 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 microM), a NO scavenger, and mimicked by 8-bromo-cyclic GMP (100 microM). 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.
Asano
S
S
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Matsuda
T
T
Takuma
K
K
Kim
H S
HS
Sato
T
T
Nishikawa
T
T
Baba
A
A
D000818:Animals; D001253:Astrocytes / Q000378:metabolism*; D001921:Brain / Q000166:cytology / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism*; D002478:Cells, Cultured; D006152:Cyclic GMP / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D008985:Monensin / Q000494:pharmacology; D009474:Neurons / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D019831:Sodium-Calcium Exchanger; D009599:Nitroprusside; D008985:Monensin; D006152:Cyclic GMP