Quisqualic acid modulates kainate responses in cultured cerebellar granule cells.
The activation of kainic acid and quisqualic acid receptors in cultured cerebellar granule cells stimulated the release of preaccumulated D-[3H]aspartate. The effect of kainate could be distinguished from that of quisqualate by its sensitivity to the antagonists kynurenic acid and 2,3-cis-piperidine dicarboxylic acid. At a concentration of kainic acid (50 microM) close to its half-maximal releasing effect, simultaneous addition of quisqualic acid (10-50 microM) resulted in a significant dose-dependent inhibition of the kainate-induced component of D-[3H]aspartate release, which was monitored by the progressive decrease in sensitivity of the evoked release to kynurenic acid. In contrast, when kainic acid was used at a subeffective concentration (10 microM), addition of low doses of quisqualate (2-5 microM) resulted in a synergistic effect on D-[3H]aspartate release. Under these conditions, the effect of the two agonists was sensitive to kynurenic acid. Kainic acid (50-100 microM) also caused a dose-dependent, kynurenic acid-sensitive accumulation of cyclic GMP (cGMP) in granule cell cultures. Quisqualic acid was, by itself, ineffective and prevented, in a dose-dependent manner, the kainate-induced cGMP formation (IC50 = 5 microM). Finally, the guanylate cyclase activator sodium nitroprusside greatly enhanced cGMP formation but had no effect on D-[3H]aspartate release. Together, these results demonstrate the existence of complex interactions between quisqualic and kainic acids and indicate that the effects of the two glutamate agonists on D-[3H]aspartate release and on cGMP accumulation are independent.
Gallo
V
V
Section of Neurobiology, Istituto Superiore di Sanità, Rome, Italy.
Giovannini
C
C
Levi
G
G
D000818:Animals; D001224:Aspartic Acid / Q000493:pharmacokinetics; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism*; D006152:Cyclic GMP / Q000378:metabolism; D004347:Drug Interactions; D007608:Kainic Acid / Q000494:pharmacology*; D009599:Nitroprusside / Q000494:pharmacology; D010069:Oxadiazoles / Q000494:pharmacology*; D016318:Quisqualic Acid; D051381:Rats; D011919:Rats, Inbred Strains
D010069:Oxadiazoles; D009599:Nitroprusside; D001224:Aspartic Acid; D016318:Quisqualic Acid; D006152:Cyclic GMP; D007608:Kainic Acid