Evidence for coupling of the kappa opioid receptor to brain GTPase

In membranes from guinea pig cerebellum, a tissue which predominantly contains kappa opioid receptors, exogenous and endogenous kappa-selective opioid agonists stimulated low-km GTPase activity by 11-20% with concentrations for half-maximal stimulation of 3-23 microM. Opioid ligands of the mu and delta type had no effect on GTPase in these membranes. Similar stimulation of GTPase by kappa opiates was obtained in rat and monkey brain membranes pretreated with beta-funaltrexamine (beta-FNA) and cis-(+/-)-3-methylfentanyl isothiocyanate (superfit) to alkylate the mu and delta receptors, respectively. The stimulation of brain GTPase by kappa opiates in both types of membranes was inhibited by naloxone with IC50's of 0.35 microM and 0.40 microM. The results demonstrate the coupling of the kappa opioid receptor to high affinity GTPase, the Ni regulatory protein of the adenylate cyclase complex.