AUTORADIOGRAPHIC LOCALIZATION OF [H-3] CYCLIC-GMP BINDING-SITES IN THE RAT-BRAIN

Both the atriopeptides and nitric oxide act in the nervous system by a ctivating guanylyl cyclases to stimulate the production of cyclic GMP. Thus a key to understanding the roles of these messengers is to under stand the functions of cyclic GMP in the nervous system. Three potenti al targets for cyclic GMP have been identified, phosphodiesterases, pr otein kinases and ion channels. In this study we describe a method usi ng autoradiography to localize specific [H-3]cGMP binding sites in the brain. The specific binding of [H-3]-cGMP to rat brain sections was s aturable (B-max = 1.5 pmol/mg protein) and of high affinity (K-D = 164 nM). The pharmacological characteristics were consistent with binding to the cGMP-dependent protein kinase. Highest densities of binding we re seen in the medial habenula, basal ganglia, locus ceruleus and nucl eus of the solitary tract. The CAI pyramidal cells of the hippocampus, the neocortex, thalamus and cerebellum were also labelled. This metho d should prove useful in studies of potential targets for cyclic GMP i n the brain.