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 [mu]M. 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 [mu]M and 0.40 [mu]M. The results demonstrate the coupling of the [kappa] opioid receptor to high affinity GTPase, the Ni regulatory protein of the adenylate cyclase complex.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/25981/1/0000047.pd