Neuropeptide FF receptors couple to a cholera toxin-sensitive G-protein in rat dorsal raphe neurones.
In rat dorsal raphe neurones, nociceptin (300 nM) reduced the peak [Ca(2+)](i) transient, triggered by depolarization, by 36.7+/-1.8% (n=46). This effect of nociceptin decreased to 16.7+/-2.9% (n=18) after pre-treatment of the neurones with pertussis toxin (5 microg/ml, 2-6 h) but was unchanged (37.4+/-2.1%, n=44) after pre-incubation with cholera toxin (5 microg/ml, 2-6 h). This suggests that, in dorsal raphe neurones, the ORL1 receptor couples to inhibitory (G(i/o)) G-proteins. The neuropeptide FF analogue, [D-Tyr1, (N-Me)Phe(3)]neuropeptide FF (10, 100, 1000 nM), acted as an anti-opioid and reduced the effect of nociceptin (300 nM, 30 s) by 62.0+/-3.3% (n=28). Following pre-incubation with cholera toxin (5 microg/ml, 2-6 h) [D-Tyr1, (N-Me)Phe3] neuropeptide FF was unable, at the three concentrations tested, to block nociceptin activity. We conclude that, in rat dorsal raphe neurones, neuropeptide FF receptors couple to stimulatory G-proteins (Gs).
Roumy
M
M
Institut de Pharmacologie et de Biologie Structurale, C.N.R.S. UMR 5089, 205 Route de Narbonne, 31077 Cedex, Toulouse, France. roumy@ipbs.fr
Zajac
J M
JM
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002772:Cholera Toxin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D019204:GTP-Binding Proteins / Q000378:metabolism*; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D011903:Raphe Nuclei / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000378:metabolism*; D000097629:Nociceptin
D002118:Calcium; D002772:Cholera Toxin; D019204:GTP-Binding Proteins; D009842:Oligopeptides; D018847:Opioid Peptides; D018013:Receptors, Neuropeptide; D000097629:Nociceptin; C083929:neuropeptide FF receptor; C105455:neuropeptide FF, Tyr(1)-N-methyl-Phe(3)-