Roles of nociceptin/orphanin FQ and nociceptin/orphanin FQ peptide receptor in respiratory rhythm generation in the medulla oblongata: an in vitro study.
BACKGROUND
Nociceptin/orphanin FQ (N/OFQ) is the endogenous agonist of the orphan opioid receptor-like receptor (NOP receptor, previously termed ORL1), a novel member of the opioid receptor family. The aim of the present study, using in vitro newborn rat preparations, was to elucidate the roles N/OFQ and the NOP receptor play in medullary generation of respiratory rhythm.


METHODS
The brainstem-spinal cord from 3-day-old Wistar rats was isolated and perfused with artificial cerebrospinal fluid (27.5 degrees C) equilibrated with oxygen 95% and carbon dioxide 5% at pH 7.4. Respiratory activity was recorded from the C4/C5 ventral roots. The effects of N/OFQ (10 nM, 30 nM, 100 nM) on respiratory frequency (fR) (bursts min(-1)) was measured. Drugs were administered through the recording chamber by means of a perfusion system. In addition, the effects of pretreatment with the classical non-selective opioid receptor antagonist naloxone 1 microM, and the selective NOP antagonist CompB 10 microM, were evaluated. Statistical significance was evaluated using ANOVA followed by Dunnett's test (P<0.05).


RESULTS
N/OFQ reduced fR in a concentration-dependent manner. Pretreatment with CompB 10 microM prevented the N/OFQ 10 nM-induced fR reduction, whereas CompB itself was inactive. Pretreatment with naloxone did not prevent the N/OFQ-induced fR reduction.


CONCLUSIONS
N/OFQ acts as a neuromodulator to reduce fR in the respiratory rhythm- generating centre of the medulla oblongata, and this action of N/OFQ is mediated by NOP receptors.
Takita
K
K
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan. ktakita@med.hokudai.ac.jp
Morimoto
Y
Y
Kemmotsu
O
O
D000818:Animals; D000831:Animals, Newborn; D046508:Culture Techniques; D004305:Dose-Response Relationship, Drug; D008526:Medulla Oblongata / Q000187:drug effects* / Q000502:physiology; D018847:Opioid Peptides / Q000494:pharmacology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000502:physiology*; D015656:Respiratory Mechanics / Q000187:drug effects* / Q000502:physiology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
D018847:Opioid Peptides; D011957:Receptors, Opioid; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat