EVIDENCE FOR COUPLING OF THE K OPIOID RECEPTOR TO BRAIN GTPase

In membranes from guinea pig cerebellum, a tissue which predominantly contains < opioid receptors, exogenous and endogenous K-selective opioid agonists stimulated low-Km GTPase activity by 11-20% with concentrations for halfmaximal stimulation of 3-23 ~M. Opioid ligands of the and ~ type had no effect on GTPase in these membranes. Similar stimulation of GTPase by K opiates was obtained in rat and monkey brain membranes pretreated with 8-funaltrexamine (8-FNA) and cis-(±)-3-methylfentanyl isothiocyanate (superfit) to alky]ate the H and 6 receptors, respectively. The stimulation of brain GTPase by opiates in both types of membranes was inhibited by naloxone with IC50's of 0.35 ~M and 0.40 ~M. The results demonstrate the coupling of the K opioid receptor to high affinity GTPase, the Ni regulatory protein of the adenylate cyclase complex.