CHRONIC ELECTROCONVULSIVE TREATMENT AUGMENTS COUPLING OF THE GTP-BINDING PROTEIN-GS TO THE CATALYTIC MOIETY OF ADENYLYL CYCLASE IN A MANNER SIMILAR TO THAT SEEN WITH CHRONIC ANTIDEPRESSANT DRUGS

A significant increase of guanylylimidodiphosphate (GppNHp)-, fluoride-, and forskolin-stimulated adenylyl cyclase was observed in synaptic membrane preparations from rat cerebral cortex subsequent to chronic electroconvulsive shock (ECS) treatment. This effect required at least five treatments over a course of 10 days. The inhibition of adenylyl cyclase induced by GppNHp was not affected by these treatments. The dissociation constant (K(D)) and maximal binding for the photoaffinity GTP analog, ]P-32[P3-(4-azidoanilido)-P1-5'-GTP(]P-32[AAGTP), to each of the synaptic membrane G proteins also were unchanged after ECS treatment. Nonetheless, the transfer of [P-32]AAGTP from G(i) to G(s), which we suggest is indicative of the coupling between G(s) and the adenylyl cyclase catalytic moiety, was accelerated by chronic ECS treatment but not by acute or sham treatment. Furthermore, chemical uncoupling of G(s) from adenylyl cyclase rendered membranes from treated animals indistinguishable from controls. Finally, in all cases tested, membranes prepared from animals subjected to chronic treatment with amitriptyline or iprindole showed similar changes in the G(s)-mediated activation of adenylyl cyclase. Acute treatments produced effects similar to controls, and liver and kidney membranes from animals receiving chronic treatment showed no changes in adenylyl cyclase despite the marked changes seen in brain. These results suggest that chronic administration of ECS enhances coupling between G(s) and adenylyl cyclase enzyme and modifies interactions between G(s) and G(i).