KAPPA-OPIOID RECEPTOR-TRANSFECTED CELL-LINES - MODULATION OF ADENYLYL-CYCLASE ACTIVITY FOLLOWING ACUTE AND CHRONIC OPIOID TREATMENTS

The opioid receptors mu, delta and kappa have recently been cloned. He re me show that kappa-agonists inhibit adenylyl cyclase activity in Ch inese hamster ovary cells stably transfected with rat kappa-opioid rec eptor cDNA. Chronic exposure of the cells to kappa-agonists did not le ad to significant desensitization of the capacity of the agonists to i nhibit adenylyl cyclase. On the other hand, withdrawal of the agonist following the chronic treatment led to the phenomenon of supersensitiv ity ('overshoot') of adenylyl cyclase activity. Both the inhibition of adenylyl cyclase activity by the acute opioid treatment and the chron ic agonist-induced supersensitivity are pertussis toxin sensitive, dem onstrating involvement of G(i)/G(o) proteins in both processes.