BETA-ADRENERGIC RECEPTORS IN RAT-BRAIN

Abstract

125I-Iodohydroxybenzylpindolol ([125I] IHYP), a potent .beta.-adrenergic receptor antagonist, was used to study .beta.-adrenergic receptors in rat brain. Binding of [125I] IHYP (30 pM) to a membrane fraction derived from cerebral cortex reached equilibrium in approximately 20 min and dissociation took place with a half time of about 16 min. Phentolamine (10-4 M) decreased non-receptor binding but it had no effect on the binding of [125I] IHYP to .beta.-adrenergic receptors in cortex, cerebellum or caudate. In the presence of phentolamine specific binding (defined as binding which was blocked by 0.3 .mu.M dl-propranolol) represented 70-85% of total binding. The binding of [125I] IHYP was inhibited by .beta.-adrenergic agonists and antagonists. d-Stereoisomers were 2-3 orders of magnitude less potent than the corresponding l-isomers. The density of [125I] IHYP binding sites was studied in membrane fractions from cerebral cortex, cerebellum and caudate nucleus by Scatchard analysis. The KD of [125I] IHYP was similar in the 3 regions studied, and the density of [125I] IHYP binding sites was approximately 50% greater in the cortex and caudate than in the cerebellum. The Hill coefficient for the binding of [125I] IHYP to membranes from cerebral cortex was 1.02. The properties of the binding of [125I] IHYP were similar to those which would be expected of binding to .beta.-adrenergic receptors in vitro.