β-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.
Proceedings of the National Academy of Sciences of the United States of America
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