Nociceptin inhibits cough in the guinea-pig by activation of ORL(1) receptors

Br J Pharmacol. 2001 Mar;132(6):1175-8. doi: 10.1038/sj.bjp.0703954.

Abstract

We studied the central and peripheral antitussive effect of ORL(1) receptor activation with nociceptin/orphanin FQ in conscious guinea-pigs. In guinea-pig cough studies, nociceptin/orphanin FQ (10, 30, and 90 microg) given directly into the CNS by an intracerebroventricular (i.c.v.) route inhibited cough elicited by capsaicin exposure by approximately 23, 29 and 52%, respectively. The antitussive activity of nociceptin/orphanin FQ (90 microg, i.c.v.) was blocked by the selective ORL(1) antagonist [Phe(1)gamma(CH(2)-NH)Gly(2)]nociceptin-(1-13)-NH(2) (180 microg, i.c.v.) and J113397 (10 mg kg(-1), i.p.) but not by the opioid antagonist, naltrexone (3 mg kg(-1), i.p.). Furthermore, intravenous (i.v.) nociceptin/orphanin FQ (1.0 and 3.0 mg kg(-1)) also inhibited cough approximately by 25 and 42%, respectively. These findings indicate that selective ORL(1) agonists display the potential to inhibit cough by both a central and peripheral mechanism, and potentially represent a novel therapeutic approach for the treatment of cough.

MeSH terms

  • Animals
  • Antitussive Agents / therapeutic use*
  • CHO Cells
  • Capsaicin
  • Cough / chemically induced
  • Cough / drug therapy*
  • Cough / metabolism
  • Cricetinae
  • Disease Models, Animal
  • Guinea Pigs
  • Male
  • Opioid Peptides / therapeutic use*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*

Substances

  • Antitussive Agents
  • Opioid Peptides
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor
  • Capsaicin