Inhibitory glutamate response on cyclic AMP formation in cultured astrocytes

Abstract

We examined the effects of glutamate receptor agonists on cyclic AMP (cAMP) formation in cultured astrocytes. L-Glutamate reduced the cAMP formation induced by either isoproterenol (IC50 7 microM) or forskolin without affecting the basal level. Glutamate agonists reduced the cAMP formation in astrocytes with the following rank order of potency: L-glutamate > trans-(+/-)-1-aminocyclopentane-1,3-dicarboxylic acid (t-ACPD) = quisqualate. Pretreatment of astrocytes with pertussis toxin resulted in a partial reduction of the glutamate response and a complete attenuation of the t-ACPD response. These results suggest that astrocytes have another type of metabotropic glutamate receptor which inhibits adenylate cyclase through pertussis toxin-sensitive G-proteins.