• K Takita, Y Morimoto, and O Kemmotsu.
• 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
• Br J Anaesth. 2003 Sep 1; 91 (3): 385389385-9.

BackgroundNociceptin/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.MethodsThe 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).ResultsN/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.ConclusionN/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.

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