AMPA RECEPTORS ARE COUPLED TO THE NITRIC-OXIDE CYCLIC-GMP PATHWAY IN CEREBELLAR ASTROGLIAL CELLS

In cultured rat cerebellar astroglia kainate induces cGMP formation wi th low potency (EC50 310 mu M). In the presence of cyclothiazide, a bl ocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor desensitization, the effect of kainate was potentiated and gl utamate and AMPA elicited large increases (>100-fold) in cGMP levels. The response to all three agonists was abolished by the nitric oxide s ynthase inhibitor N-G-nitro-L-arginine and required extracellular calc ium. Uptake of Co2+ was induced by AMPA in a limited population of ast roglial cells and this effect was potentiated by cyclothiazide. These results indicate that calcium-permeable AMPA receptors mediate stimula tion of nitric oxide formation in cerebellar astroglia. This effect ma y be relevant for glutamate-dependent synaptic plasticity processes in the cerebellum.