Lithium does not prevent agonist-induced subsensitivity of human adenylate cyclase.
In a previous study 11 depressed patients were treated with salbutamol, a beta-2 adrenergic agonist, and beta-2 adrenergic receptor sensitivity was evaluated by measuring the plasma cyclic AMP rise after an iv dose of salbutamol. Salbutamol treatment induced subsensitivity of the beta-adrenergic adenylate cyclase with a time course paralleling the antidepressant effects. In the present study nine patients who were depressed despite treatment with lithium were treated with salbutamol plus lithium. Subsensitivity of the beta-adrenergic adenylate cyclase developed in the presence of lithium to the same degree as in patients treated with salbutamol alone. These results represent the first human study of the theory that lithium stabilizes receptor sensitivity changes. Lithium's failure to prevent subsensitivity agrees with reports that lithium fails to prevent impramine-induced subsensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity of beta-adrenergic receptors in rat cortex. Lithium stabilization of receptor sensitivity would therefore appear to be unidirectional, preventing supersensitivity but not subsensitivity.
D000262:Adenylyl Cyclases / Q000097:blood*; D000328:Adult; D000368:Aged; D000420:Albuterol / Q000494:pharmacology* / Q000627:therapeutic use; D000818:Animals; D001714:Bipolar Disorder / Q000188:drug therapy / Q000523:psychology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D000242:Cyclic AMP / Q000097:blood; D003866:Depressive Disorder / Q000188:drug therapy* / Q000523:psychology; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006801:Humans; D007099:Imipramine / Q000494:pharmacology; D008094:Lithium / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D008875:Middle Aged; D010555:Personality Inventory; D051381:Rats; D011941:Receptors, Adrenergic / Q000187:drug effects*; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*
D011941:Receptors, Adrenergic; D011943:Receptors, Adrenergic, beta; D008094:Lithium; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D007099:Imipramine; D000420:Albuterol