Effects of sigma ligands on the nociceptin/orphanin FQ receptor co-expressed 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 the cloned nociceptin/orphanin FQ receptor and GIRK1 mRNAs. Carbetapentane and rimcazole, which induced no current response at 100 microM, reversibly suppressed the inward K+ current responses induced by nociceptin in a concentration-dependent manner, and the IC50 values (microM) 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 microM, 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.
Kobayashi
T
T
Department of Molecular Neuropathology, Niigata University, Japan.
Ikeda
K
K
Togashi
S
S
Itoh
N
N
Kumanishi
T
T
D000818:Animals; D002227:Carbazoles / Q000494:pharmacology*; D003517:Cyclopentanes / Q000494:pharmacology*; D019204:GTP-Binding Proteins / Q000378:metabolism; D009292:Narcotic Antagonists; D009865:Oocytes / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology; D015221:Potassium Channels / Q000502:physiology*; D051381:Rats; D011957:Receptors, Opioid / Q000502:physiology; D017480:Receptors, sigma; D014981:Xenopus; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D002227:Carbazoles; D003517:Cyclopentanes; D019204:GTP-Binding Proteins; D009292:Narcotic Antagonists; D018847:Opioid Peptides; D015221:Potassium Channels; D011957:Receptors, Opioid; D017480:Receptors, sigma; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C018861:carbetapentane; C034931:rimcazole