Guanosine triphosphate: an endogenous compound in the rabbit cerebellar cortex which couples the beta-adrenergic...

The guanyl nucleotides GTP and GDP are endogenous factors in the rabbit cerebellum which contribute to the in vitro coupling of the beta-adrenergic receptor to adenylate cyclase. Repeated washing of the particulate material removes these endoactivity to beta-adrenergic agonists. The endogenous GTP and GDP, isolated by high pressure liquid chromatography, mimic the ability of the supernatant both to restore the coupling of receptor and enzyme and to increase basal enzyme activity. The effectiveness of GDP reflects its conversion to GTP during the assay. GTP does not affect either the number of [3H]dihydroalprenolol binding sites or the affinity of these sites for L-isoproterenol; furthermore, GTP does not cause a shift in activation affinity of enzyme activity for isoproterenol. Thus, the guanyl nucleotides are endogenous constituents of the mammalian brain which are essential for the functional 'coupling' of beta-adrenergic receptors to adenylate cyclase.