Evidence for coupling of the κ opioid receptor to brain GTPase

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