Na + ions and Gpp(NH)p selectively inhibit agonist interactions at μ- and κ-opioid receptor sites in rabbit and guinea-pig cerebellum membranes

Abstract

Rabbit and guinea-pig cerebellum membrane preparations contain a high proportion (> 80%) of μ- and of κ-opioid binding sites, respectively. These preparations were therefore used to compare the regulation of binding of μ- and of κ-opioid agonists and antagonists by sodium ions and by guanyl-5′-yl imidodiphosphate. We report here that Na + ions, Gpp(NH)p and most efficiently, the two agents in association selectively inhibited binding of opioid agonists not only in the μ preparation (rabbit cerebellum) but also in the κ preparaion (guinea-pig cerebellum). These allosteric effectors did not inhibit equilibrium binding of antagonists (naloxone, Mr 2266 or diprenorphine) in the two preparations. Taken together these results suggest that occupancy either of the μ-receptor by a μ-agonist or of the κ-receptor by a κ-agonist may be accompanied by similar if not identical molecular events. They also suggest a method to rapidly screen newly designed drugs as μ- or κ-opioid agonists or antagonists.