Molecular Pharmacology, Vol 10, 736-745, Copyright © 1974 by the American Society for Pharmacology and Experimental Therapeutics

Interactions between -Aminobutyric Acid and Guanosine Cyclic 3',5'-Monophosphate in Rat Cerebellum

¹ Laboratory of Preclinical Pharmacology, National Institute of Mental Health, Saint Elizabeths Hospital, Washington, D. C. 20032

The concentrations of adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 3',5'-cyclic monophosphate (cGMP) were measured in various brain areas of rats either kept at 22° or exposed to 4° for various periods. Brain metabolic activity was terminated by focusing a microwave beam (70 mW/cm²) on the skull for 2 sec. Pituitary was the only tissue in which cAMP concentration was increased by exposure to cold. The concentrations of cGMP in cerebellum, hypothalamus, and brain stem were significantly increased between 5 and 15 min of exposure to 4°. The increase in cerebellar cGMP elicited by cold was prompt but transient. When rats were exposed to cold, cerebellar cGMP content increased 3-fold over the control value in 5 min and returned to basal level after 30 min of cold exposure. This increase of cerebellar cGMP was unimpaired when cholinergic, catecholaminergic, and serotonergic neuronal mechanisms were blocked pharmacologically. Of the three drugs —aminooxyacetic acid, hydrazine sulfate, and hydroxylamine—which increase cerebellar concentrations of -aminobutyric acid (GABA), the first two inhibited the increase in cGMP concentration elicited by cold exposure. The inhibition of the increment in cerebellar cGMP elicited by cold correlated with the extent of the increase in cerebellar GABA concentrations. Isonicotinic acid hydrazide decreased the concentration of cerebellar GABA and caused an increase of cGMP concentration in the cerebellum of rats either kept at 22° or exposed to cold for 5 min. This drug, up to 10 mM, failed to inhibit the cyclic nucleotide phosphodiesterase activity of brain homogenates. The increase or decrease of cerebellar concentrations of GABA elicited pharmacologically failed to change the concentrations of cAMP in cerebellum.