title: Nociceptin/orphanin FQ slows inspiratory rhythm via its direct effects on the pre-Bötzinger complex.
abstract: In a previous study, we showed that in an in vitro en bloc preparation of newborn rats perfused with standard [K(+)] (6.2mM) and high [K(+)] (11.2mM) artificial cerebrospinal fluid (aCSF), nociceptin/orphanin FQ (N/OFQ) suppresses bursting of pre-inspiratory neurons with 1:1 coupling to the fictive inspiration. However, it is unclear whether the pre-Bötzinger complex (preBötC) is involved in the N/OFQ-induced slowing. Using in vitro en bloc preparations with and without the retrotrapezoid nucleus/parafacial respiratory group (RTN/pFRG) perfused with high [K(+)] aCSF, we found the following: (1) there were no differences in the effects of N/OFQ on the inspiratory rhythm between the preparations with and without the RTN/pFRG, (2) N/OFQ decreased the input resistance of inspiratory neurons (Insps) in the preparations without the RTN/pFRG and suppressed their ectopic firing activities, and (3) N/OFQ suppressed the spontaneous firing of Insps under a chemical synaptic transmission blockade. In conclusion, it is possible that the preBötC is involved in N/OFQ-induced inspiratory rhythm slowing.
authors.affiliation: Department of Anesthesiology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan. Electronic address: ktakita@med.hokudai.ac.jp.
authors.forename: Koichi
authors.initials: K
authors.lastname: Takita
authors.affiliation: Department of Anesthesiology, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo, 060-8638, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Morimoto
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001640:Bicuculline / Q000031:analogs & derivatives / Q000494:pharmacology; D002110:Caffeine / Q000494:pharmacology; D000697:Central Nervous System Stimulants / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D058787:GABA-A Receptor Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects*; D018847:Opioid Peptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D010507:Periodicity; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D012125:Respiratory Center / Q000166:cytology* / Q000187:drug effects*; D014970:Xanthines / Q000494:pharmacology; D000097629:Nociceptin
chemical_list: D001640:Bicuculline; D002110:Caffeine; D000697:Central Nervous System Stimulants; D058787:GABA-A Receptor Antagonists; D018847:Opioid Peptides; D011188:Potassium; D014970:Xanthines; D000097629:Nociceptin; C008514:methylxanthine; C017069:bicuculline methiodide
keywords: Brainstem; Nociceptin/orphanin FQ; Pre-Bötzinger complex; Respiratory rhythm generation; Retrotrapezoid nucleus/parafacial respiratory group