Regulation of CNS alpha- and beta-adrenergic receptor function may play a significant role in CNS disease states. Altered functional state of central adrenergic synapses, which current therapy aims to reverse, may be involved in affective disorders and hypertension. Understanding normal CNS adrenergic receptor mechanisms and regulation is clearly of prime importance. Techniques are now available for the biochemical study of adrenergic receptors. Previous results: radio-labeling of alpha-receptors has indicated 1) two CNS alpha-receptor popultions, one (alpha 1) labeled by the 3H-antagonists WB-4101 and dihydroergokryptine (DHE), and the other (alpha 2) labeled by the 3H-agonists epinephrine, norepinephrine (NE) and cloidine, and DHE; 2) the CNS alpha 1 and alpha 2 receptors are pharmacologically similar to the peripheral postsynaptic and presynaptic alpha-receptors respectively, but 3) neither CNS alpha-receptor is significantly located on NE terminals, and both are up-regulated by NE depletion; 4) agonist affinities at the alpha 2, but not the alpha 1 receptor are lowered by GTP and sodium, suggesting, c.f. the beta-receptor, that alpha 2 but not alpha 1 receptors are coupled to adenylate cyclase and can be down-regulatd; 5) 3H-EPI and 3H-dihydroalprenolol both label a cerebellar beta 2 receptor which is GTP-insensitive, but Na ion-sensitive. Preliminary results: divalent cations counteract the effect of GTP at alpha 2 receptors, and by implication may uncouple alpha 2 receptors from adenylate cycase; alpha 2 receptor GTP-sensitivity varies with species, and in rat CNS there are 2 subtypes of alpha 2 receptor with different GTP sensitivities; CNS alpha-receptors can covalently photoaffinity labeled with H-catecholamines. Objectives: 1) to examine coupling and desensitization mechanisms of CNS adrenergic receptor sites; 2) to localize CNS alpha 1 and alpha 2 sites in glial and neuronal cells, and pre- and postsynaptic membranes by cell fractionation and comparative ontogenetic studies; 3) to reversibly and covalently label CNS alpha and beta receptors in purifies and solubilized membranes; 4) to correlate in several species differential CNS alpha 1, alpha 2 and beta 2 receptor binding properties and alpha- and beta-receptor coupled adenylate cyclase activity in CNS homogenates.