Excitatory amino acid receptors and guanosine 3',5'-cyclic monophosphate in incubated slices of immature and adult rat cerebellum

Abstract

Addition of the excitatory amino acids l-glutamate, l-aspartate and their analogues kainate and N-methyl-d-aspartate to incubated slices of adult rat cerebellum led to large increases in cyclic GMP levels. The order of apparent potencies was kainate greater than N-methyl-d-aspartate greater than glutamate and aspartate. D-alpha-aminoadipate and Mg2-+ inhibited responses to N-methyl-d-aspartate while glutamic acid diethyl ester was most effective against those to glutamate; responses to kainate were least affected by the antagonists. The exicitant amino acids also elicited large elevations of cyclic GMP levels in slices of immature (8 day) cerebellum. Kainate was less effective than in adult but induced two responses distinguishable by their different time courses, concentration dependencies and sensitivity to antagonists. N-methyl-d-aspartate, glutamate and aspartate were 5 to 10-fold more potent than in the adult. Responses to N-methyl-d-aspartate were similarly inhibited by d-alpha-aminoadipate and Mg2+ but those to glutamate were more resistant to glutamic acid diethyl ester than in the adult. It is concluded that the accumulation of cyclic GMP in response to excitant amino acids in the adult cerebellum is mediated via the operation of receptor types showing pharmacological characteristics expected of excitatory amino acid receptors. The actions of kainate in the immature cerebellum appear to be mediated by receptors different from those on which it acts primarily in the adult.