British Journal of Anaesthesia, 2003, Vol. 91, No. 3 385-389
© 2003 The Board of Management and Trustees of the British Journal of Anaesthesia
Laboratory Investigations |
Roles of nociceptin/orphanin FQ and nociceptin/orphanin FQ peptide receptor in respiratory rhythm generation in the medulla oblongata: an in vitro study
Department of Anesthesiology and Critical Care Medicine, Hokkaido University Graduate School of Medicine, Kita-15, Nishi-7, Kita-ku, Sapporo 060-8638, Japan
Corresponding author. E-mail: ktakita@med.hokudai.ac.jp
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°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 µM, and the selective NOP antagonist CompB 10 µM, 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 µM 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.
Conclusion. 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.
Br J Anaesth 2003; 91: 385–9
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