ROLES OF CYCLIC AMP AND CYCLIC GMP IN THE CEREBELLUM

Publisher Summary This chapter discusses a study to investigate the role of cyclic AMP and cyclic GMP in the cerebellum. Following intracerebroventricular injection of IPTBO into mice, changes in the concentrations of cyclic AMP and cyclic GMP in the cortex, subcortex, and cerebellum were observed with the most pronounced and significant changes being in the cerebellum where cyclic AMP concentrations decreased and those of cyclic GMP increased. Pentobarbitone (i.p.) produced opposite changes and blocked the changes produced by IPTBO. Caffeine and soman, which have convulsant activity, produced some similar changes to IPTBO. The results could be explained by a neuronal pathway in the cerebellum involving a GABA-activated adenylate cyclase and an ACh-activated guanylate cyclase. These enzymic activities were demonstrated using cerebellar tissue from the rat. IPTBO and other convulsant putative GABA antagonists, N -methyl bicuculline and picrotoxin, blocked the GABA-activation of the adenylate cyclase, whereas diazepam and pentobarbitone that can prevent the convulsions produced by IPTBO mimicked the action of GABA. The anticholinergics, atropine and aprophen, blocked the ACh-activation of the guanylate cyclase.