BETA-ADRENERGIC-RECEPTOR REGULATION BY AGONISTS AND MEMBRANE DEPOLARIZATION IN RAT-BRAIN SLICES

Rat cerebral cortex slices exposed to (-)-isoproterenol and then washed accumulated significantly less cyclic AMP when rechallenged with isoproterenol than did control slices. The isoproterenol-induced desensitization was associated with a concurrent reduction in [3H]dihydroalprenolol membrane binding but with no change in the affinity of [3H]dihydroalprenolol or isoproterenol for the binding sites. β-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, bactrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetrodotoxin or by removing Na+ from the buffer. These data demonstrate partial participation of the membrane receptor in β-adrenergic desensitization of rat brain slices and suggest that brain β-adrenergic receptors, like cholinergic receptors in skeletal muscle and α-adrenergic receptors in rat parotid, are regulated in part by membrane voltage.