Abstract
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. .beta.-Adrenergic receptor desensitization was rapidly reversed by slice depolarization with high-[K+] buffers, batrachotoxin, grayanotoxin, or veratridine, even in the continued presence of isoproterenol. Restoration of binding by grayanotoxin was prevented by tetradotoxin or by removing Na+ from the buffer. Partial participation of the membrane receptor in .beta.-adrenergic desensitization of rat brain slices was demonstrated and brain .beta.-adrenergic receptors, like cholinergic receptors in skeletal muscle and .alpha.-adrenergic receptors in rat parotid, may be regulated in part by membrane voltage.