title: Neuropeptide FF receptors exhibit direct and anti-opioid effects on mice dorsal raphe nucleus neurons.
abstract: By using acutely dissociated dorsal raphe nucleus neurons (DRN) from young mice, direct and anti-opioid effects of Neuropeptide FF (NPFF) receptors were measured. The NPFF analog 1 DMe (10 µM) had no effect on resting Ca2+ channels but reduced the magnitude of Ca2+ transients induced by depolarization in 83.3% neurons tested, of which the inhibition rate is 45.4±2.9%. Pertussis toxin treatment reduced to 18.9% the number of responding neurons and attenuated by 47% the response of 1 DMe. In contrast, cholera toxin treatment had no significant effect. Eighteen minute perfusion with 1 DMe at a very low 10 nM concentration, that did not directly inhibit Ca2+ transients triggered by depolarization in every neuron, attenuated by 78% the inhibitory effect of Nociceptin/orphanin FQ (N/OFQ) on Ca2+ transients, but not that of by serotonin. These results demonstrated for the first time that NPFF receptors on mice DRN inhibit Ca2+ transients induced by depolarization via Gi/o protein and also exhibit a specific anti-opioid activity on nociceptin receptors, and that their specific anti-opioid activity is not a direct consequence of their activity on Ca2+ transients.
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, CNRS / Université de Toulouse, UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Ding
authors.affiliation: Institut de Pharmacologie et de Biologie Structurale, CNRS / Université de Toulouse, UMR 5089, 205 route de Narbonne, 31077 Toulouse Cedex, France. Electronic address: jean-marie.zajac@ipbs.fr.
authors.forename: Jean-Marie
authors.initials: JM
authors.lastname: Zajac
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology; D002772:Cholera Toxin / Q000494:pharmacology; D065847:Dorsal Raphe Nucleus / Q000166:cytology*; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D018847:Opioid Peptides / Q000494:pharmacology; D037342:Pertussis Toxin / Q000494:pharmacology; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000502:physiology*; D011957:Receptors, Opioid / Q000502:physiology*; D012701:Serotonin / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D002118:Calcium; D002772:Cholera Toxin; D009842:Oligopeptides; D018847:Opioid Peptides; D037342:Pertussis Toxin; D018013:Receptors, Neuropeptide; D011957:Receptors, Opioid; D012701:Serotonin; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C083929:neuropeptide FF receptor; C105455:neuropeptide FF, Tyr(1)-N-methyl-Phe(3)-; C000722287:Oprl1 protein, mouse
keywords: Anti-opioid activity; Ca(2+); Dorsal raphe nucleus; Neuropeptide FF; Nociceptin receptor; Serotonin