Effects of lithium on the beta-adrenergic receptor-adenylate cyclase system in rat cerebral cortical membranes.
The effects of lithium on the beta-adrenoceptor-adenylate cyclase system in cerebral cortical membranes of rats were investigated. Lithium chloride inhibited adenylate cyclase activity in a concentration-dependent manner in vitro. However, relatively high concentrations of lithium were needed for this inhibition; and at 1 mM, no significant reduction in adenylate cyclase activity was seen under any condition. Administration of lithium carbonate for 21 days decreased the maximum number of [3H]dihydroalprenolol binding sites without changing the apparent dissociation constant. Activation of adenylate cyclase by (-)-isoproterenol in the presence of 1 microM guanyl-5'-ylimidodiphosphate (Gpp(NH)p) was significantly attenuated in lithium-treated rats compared with the controls. Lithium treatment reduced the Gpp(NH)p-stimulated adenylate cyclase activity in the presence of 10 microM (-)-isoproterenol, but not in the absence of this beta-adrenergic receptor agonist. Basal activity or adenylate cyclase activity stimulated by forskolin or manganese was not affected, whereas the activity stimulated by sodium fluoride was significantly attenuated by long-term lithium treatment. These results indicate that chronic lithium treatment induces subsensitivity in the beta-adrenoceptor-adenylate cyclase system, for which down-regulation of beta-adrenergic receptors is chiefly responsible.
Odagaki
Y
Y
Department of Psychiatry and Neurology, Hokkaido University School of Medicine, Sapporo, Japan.
Koyama
T
T
Matsubara
S
S
Yamashita
I
I
D000067956:Adenylyl Cyclase Inhibitors; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects* / Q000201:enzymology; D002712:Chlorides; D005576:Colforsin / Q000494:pharmacology; D004082:Dihydroalprenolol / Q000494:pharmacology; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D011943:Receptors, Adrenergic, beta / Q000187:drug effects*; D012969:Sodium Fluoride / Q000494:pharmacology
D000067956:Adenylyl Cyclase Inhibitors; D002712:Chlorides; D017895:Manganese Compounds; D011943:Receptors, Adrenergic, beta; D005576:Colforsin; D008345:Manganese; D004082:Dihydroalprenolol; D012969:Sodium Fluoride; D008094:Lithium; C025340:manganese chloride