Efflux of 45calcium from cultured primary astrocytes: effects of glutamate receptor agonists and antagonists.
The effects of high-K, glutamate and glutamate receptor agonists on the efflux of Ca2+ were studied in cultured primary astrocytes, prepared from the brains of newborn rats. An increase in efflux of 45Ca2+ of produced by a large extracellular concentration of K+ was effectively inhibited by verapamil, a blocker of voltage-gated Ca2+ channels, suggesting that these cells have functional voltage-sensitive Ca2+ channels. Glutamate and its agonists kainate, quisqualate and N-methyl-D-aspartate (NMDA) stimulated the efflux of preloaded 45Ca2+, in a dose-dependent manner. The most effective agonist was quisqualate followed by glutamate, whereas kainate and NMDA were less potent. In the Mg-free medium, the response to NMDA was significantly increased. The quisqualate receptor agonist (RS)-alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) also stimulated the efflux, about equally effectively as quisqualate. The glutamate-, quisqualate- and kainate-induced efflux of 45Ca2+ was significantly inhibited by L-glutamatediethylester (GDEE) and that of NMDA by DL-2-amino-5-phosphonopentanoic acid (AP5). The kainate-induced efflux was totally inhibited by verapamil, but that of glutamate only partially. No effect of verapamil was observed on the quisqualate-induced efflux of 45Ca2+. The results imply that, in cultured astrocytes, Ca2+ fluxes induced by glutamate agonists, occur partially through voltage-dependent Ca2+ channels. The extensive release of 45Ca2+ caused by quisqualate was mainly due to a release from internal stores.
Holopainen
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Department of Biomedical Sciences, University of Tampere, Finland.
Akerman
K E
KE
D000818:Animals; D000831:Animals, Newborn / Q000502:physiology; D001253:Astrocytes / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism*; D002132:Calcium Radioisotopes; D002478:Cells, Cultured; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates / Q000494:pharmacology; D007608:Kainic Acid / Q000494:pharmacology; D016202:N-Methylaspartate / Q000494:pharmacology; D016318:Quisqualic Acid / Q000494:pharmacology; D051381:Rats; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter / Q000502:physiology*; D014633:Valine / Q000031:analogs & derivatives / Q000494:pharmacology
D002132:Calcium Radioisotopes; D018691:Excitatory Amino Acid Antagonists; D005971:Glutamates; D017470:Receptors, Glutamate; D017981:Receptors, Neurotransmitter; C011829:glutamic acid diethyl ester; D016202:N-Methylaspartate; C056639:2-amino-5-phosphopentanoic acid; D016318:Quisqualic Acid; D014633:Valine; D007608:Kainic Acid; D002118:Calcium