Effects of σ ligands on the nociceptin/orphanin FQ receptor co-expressed with the G-protein-activated K⁺ channel in Xenopus oocytes

Abstract

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 σ ligands on the nociceptin/orphanin FQ receptor in Xenopus oocytes co-injected with the cloned nociceptin/orphanin FQ receptor and GIRK1 mRNAs. Carbetapentane and rimcazole, which induced no current response at 100 μM, reversibly suppressed the inward K⁺ current responses induced by nociceptin in a concentration-dependent manner, and the IC₅₀ values (μM) for these compounds were 9.0 and 12.6, respectively. (±)-N-allylnormetazocine, (+)-cyclazocine, (+)-3-(3-hydroxyphenyl)-N-(1-propyl)piperidine and 1,3-di-(2-tolyl)guanidine, at 100 μM, had no effect on the receptor. These results suggest that carbetapentane and rimcazole act as antagonists at the nociceptin/orphanin FQ receptor and may be involved in pain regulation.

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