AMPA Receptors are Coupled to the Nitric Oxide/Cyclic GMP Pathway in Cerebellar Astroglial Cells

In cultured rat cerebellar astroglia kainate induces cGMP formation with low potency (EC50 310 microM). In the presence of cyclothiazide, a blocker of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA) receptor desensitization, the effect of kainate was potentiated and glutamate and AMPA elicited large increases (> 100-fold) in cGMP levels. The response to all three agonists was abolished by the nitric oxide synthase inhibitor N(G)-nitro-L-arginine and required extracellular calcium. Uptake of Co2+ was induced by AMPA in a limited population of astroglial cells and this effect was potentiated by cyclothiazide. These results indicate that calcium-permeable AMPA receptors mediate stimulation of nitric oxide formation in cerebellar astroglia. This effect may be relevant for glutamate-dependent synaptic plasticity processes in the cerebellum.