Role of Na(+)-Ca2+ exchanger in agonist-induced Ca2+ signaling in cultured rat astrocytes.
We have previously demonstrated that activation of the Na(+)-Ca2+ exchanger in the reverse mode causes Ca2+ influx in astrocytes. In addition, we showed that the exchange activity was stimulated by nitric oxide (NO)/cyclic GMP and inhibited by ascorbic acid. The present study demonstrates that the Na(+)-Ca2+ exchanger is involved in agonist-induced Ca2+ signaling in cultured rat astrocytes. The 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 the ionomycin-induced increase in [Ca2+]i. The NA-induced Ca2+ signal was also attenuated by S-nitroso-L-cysteine and 8-bromo cyclic GMP, whereas it was enhanced by 3,4-dichlorobenzamil, an inhibitor of the Na(+)-Ca2+ exchanger. Treatment of astrocytes with antisense, but not sense, deoxynucleotides to the sequence encoding the Na(+)-Ca2+ exchanger enhanced the ionomycin-induced increase in [Ca2+]i and blocked the effects of SNP and 8-bromo cyclic GMP in reducing the NA-induced Ca2+ signal. Furthermore, the 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 that the exchanger plays a role in Ca2+ efflux when [Ca2+]i is raised above basal levels in astrocytes.
Takuma
K
K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Osaka University, Japan.
Matsuda
T
T
Hashimoto
H
H
Kitanaka
J
J
Asano
S
S
Kishida
Y
Y
Baba
A
A
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001483:Base Sequence; D003994:Bucladesine / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism*; D002352:Carrier Proteins / Q000819:agonists / Q000096:biosynthesis / Q000378:metabolism*; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology / Q000378:metabolism; D006152:Cyclic GMP / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D003545:Cysteine / Q000031:analogs & derivatives / Q000494:pharmacology; D018698:Glutamic Acid / Q000494:pharmacology; D015759:Ionomycin / Q000494:pharmacology; D007700:Kinetics; D009569:Nitric Oxide / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology*; D009638:Norepinephrine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D026403:S-Nitrosothiols; D015398:Signal Transduction / Q000187:drug effects; D019831:Sodium-Calcium Exchanger
D002352:Carrier Proteins; D016376:Oligonucleotides, Antisense; D010716:Phosphatidylinositols; D026403:S-Nitrosothiols; D019831:Sodium-Calcium Exchanger; C041470:3',4'-dichlorobenzamil; D009599:Nitroprusside; C016276:8-bromocyclic GMP; D009569:Nitric Oxide; D018698:Glutamic Acid; D015759:Ionomycin; D003994:Bucladesine; D000584:Amiloride; D000255:Adenosine Triphosphate; C021315:S-nitrosocysteine; D006152:Cyclic GMP; D003545:Cysteine; D002118:Calcium; D009638:Norepinephrine