AGONIST-INDUCED CHANGES IN BETA-ADRENERGIC-RECEPTOR DENSITY AND RECEPTOR-MEDIATED RESPONSIVENESS IN SLICES OF RAT CEREBRAL-CORTEX

Abstract

Incubation of slices of rat cerebral cortex with the .beta. adrenergic receptor agonist (-)-isoproterenol led to a 30 to 50% decrease in the number of binding sites for [125I]iodohydroxybenzylpindolol and to a 60 to 80% decrease in isoproterenol-stimulated cyclic AMP accumulation. The density of .beta. adrenergic receptors was also decreased following incubation with (-)-norepinephrine but not with (+)-isoproterenol or dopamine and the decrease in receptor density was blocked by co-incubation with the .beta. adrenergic receptor antagonist sotalol. The half-time for loss of receptors was approximately 3 min and recovery was observed during a 1 h reincubation of tissue slices or following exposure to guanine nucleotides. A decrease in .beta. adrenergic receptor density was also observed following chronic treatment with desmethylimipramine which blocks norepinephrine reuptake and potentiates the effects of neurally released norepinephrine at adrenergic receptors. The loss of receptors induced in vitro could be reversed by reincubation or by exposure to guanine nucleotides. The loss of receptors induced in vivo was not affected by these procedures.