title: Direct influence of antidepressants on GTP binding protein of adenylate cyclase in cell membranes of the cerebral cortex of rats.
abstract: Recently, it has been suggested that antidepressant drugs exert their pharmacological action through functional changes in the adrenergic-receptor coupled adenylate cyclase system. In the present research, we examined the direct effects of antidepressants on adenylate cyclase (A-cyclase) activity by in vitro incubation of cell membranes from the cerebral cortex of rats with these drugs. All antidepressants examined, such as imipramine, clomipramine, amitriptyline, desipramine, mianserin and zimelidine inhibited A-cyclase in a dose dependent manner. Antidepressants did not exert any influence on Mn2+-induced elevation of A-cyclase, but significantly suppressed F(-)-stimulated A-cyclase activity. GTP-induced elevation of A-cyclase was completely inhibited by prior incubation with antidepressants. Our conclusion, therefore, is that antidepressants may reduce A-cyclase activity not by inhibiting the function of the catalytic unit of A-cyclase, but by suppressing the N-protein function.
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology*; D001923:Brain Chemistry / Q000187:drug effects*; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D002712:Chlorides; D002746:Chlorpromazine / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006160:Guanosine Triphosphate / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D008345:Manganese / Q000494:pharmacology; D017895:Manganese Compounds; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000494:pharmacology; D013347:Subcellular Fractions / Q000187:drug effects / Q000378:metabolism
chemical_list: D000928:Antidepressive Agents; D002712:Chlorides; D017895:Manganese Compounds; D008345:Manganese; D006160:Guanosine Triphosphate; D012969:Sodium Fluoride; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases; C025340:manganese chloride; D002746:Chlorpromazine