Enhanced Stimulatory Adenylyl Cyclase Signaling during Opioid Dependence Is Associated with a Reduction in

Chronic opioid treatment of stably m-opioid receptor trans-fected human mammary epidermoid A431 carcinoma cells (clone A431/m13) results in sensitization of adenylyl cyclase (AC), a cellular adaptation associated with drug dependence. Up-regulation of AC is characterized by significantly increased levels of both basal and post-receptor-stimulated effector ac-tivities, which develop without any apparent change in the quantity of stimulatory G proteins and the maximum catalytic activity of AC. Here, we report that detergent extracts from membranes of chronically morphine-treated (10 mM; 2 days) A431/m13 cells display higher stimulatory AC activities as as-sessed in the S49cyc2 reconstitution assay. This finding is most likely due to an increased functional activity of Gsa be-cause the addition of exogenous Gbg subunits, which per se stimulate AC in S49cyc2 membranes, failed to affect the dif