Roles of nociceptin/orphanin FQ and nociceptin/orphanin FQ peptide receptor in respiratory rhythm generation in the medulla oblongata: an in vitro study

Br J Anaesth. 2003 Sep;91(3):385-9. doi: 10.1093/bja/aeg191.


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.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Culture Techniques
  • Dose-Response Relationship, Drug
  • Medulla Oblongata / drug effects*
  • Medulla Oblongata / physiology
  • Opioid Peptides / pharmacology*
  • Opioid Peptides / physiology
  • Rats
  • Rats, Wistar
  • Receptors, Opioid / physiology*
  • Respiratory Mechanics / drug effects*
  • Respiratory Mechanics / physiology


  • Opioid Peptides
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor