EFFECTS OF SIGMA-LIGANDS ON THE NOCICEPTIN ORPHANIN FQ RECEPTOR COEXPRESSED WITH THE G-PROTEIN-ACTIVATED K+ CHANNEL IN XENOPUS OOCYTES/

Taking advantage of the functional coupling of the nociceptin/orphanin FQ receptor with the G-protein-activated inwardly rectifying K+ (GIRK ) channel, we investigated the effects of various sigma ligands on the nociceptin/orphanin FQ receptor in Xenopus oocytes co-injected with t he cloned nociceptin/orphanin FQ receptor and GIRK1 mRNAs. Carbetapent ane and rimcazole, which induced no current response at 100 mu M, reve rsibly suppressed the inward K+ current responses induced by nocicepti n in a concentration-dependent manner. and the IC50 values (mu M) for these compounds were 9.0 and 12.6, respectively. (+/-)-N-allylnormetaz ocine, (+)-cyclazocine, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and 1,3-di-(2-tolyl)guanidine, at 100 mu M, had no effect on the rece ptor. These results suggest that carbetapentane and rimcazole act as a ntagonists at the nociceptin/orphanin FQ receptor and may be involved in pain regulation.