Nociceptin/orphanin FQ inhibits capsaicin-induced guinea-pig airway contraction through an inward-rectifier potassium channel

Br J Pharmacol. 2002 Feb;135(3):764-70. doi: 10.1038/sj.bjp.0704515.

Abstract

Nociceptin/orphanin FQ (N/OFQ), an endogenous opioid-like orphan receptor (NOP receptor, previously termed ORL1 receptor) agonist, has been found to inhibit capsaicin-induced bronchoconstriction in isolated guinea-pig lungs and in vivo. The underlying mechanisms are not clear. In the present studies, we tested the effect of N/OFQ on VR1 channel function in isolated guinea-pig nodose ganglia cells. Capsaicin increased intracellular Ca(2+) concentration in these cells through activation of vanilloid receptors. Capsaicin-induced Ca(2+) responses were attenuated by pretreatment of nodose neurons with N/OFQ (1 microM). N/OFQ inhibitory effect on the Ca(2+) response in nodose ganglia cells was antagonized by tertiapin (0.5 microM), an inhibitor of inward-rectifier K(+) channels, but not by verapamil, a voltage gated Ca(2+) channel blocker, indicating that an inward-rectifier K(+) channel is involved in N/OFQ inhibitory effect. In isolated guinea-pig bronchus, N/OFQ (1 microM) inhibited capsaicin-induced airway contraction. Tertiapin (0.5 microM) abolished the N/OFQ inhibition of capsaicin-induced bronchial contraction. Capsaicin (10 microg) increased pulmonary inflation pressure in the isolated perfused guinea-pig lungs. This response was significantly attenuated by pretreatment with N/OFQ (1 microM). Tertiapin also abolished the N/OFQ inhibitory effect on capsaicin-induced bronchoconstriction in perfused lungs. Capsaicin increased the release of substance P and neurokinin A from isolated lungs. N/OFQ (1 microM) blocked the capsaicin-induced tachykinin release. These results indicate that N/OFQ-induced hyperpolarization of tachykinin containing airway sensory nerves, through an inward-rectifier K(+) channel activation, accounts for the inhibition of capsaicin-evoked broncoconstriction.

MeSH terms

  • Animals
  • Bronchi / drug effects*
  • Bronchi / physiology
  • Bronchoconstriction / drug effects*
  • Bronchoconstriction / physiology
  • Capsaicin / antagonists & inhibitors
  • Capsaicin / pharmacology*
  • Guinea Pigs
  • In Vitro Techniques
  • Lung / drug effects*
  • Lung / physiology
  • Male
  • Nociceptin
  • Nodose Ganglion / cytology
  • Nodose Ganglion / drug effects
  • Nodose Ganglion / physiology
  • Opioid Peptides / pharmacology
  • Opioid Peptides / physiology*
  • Potassium Channels, Inwardly Rectifying / agonists
  • Potassium Channels, Inwardly Rectifying / antagonists & inhibitors
  • Potassium Channels, Inwardly Rectifying / physiology*
  • Tachykinins / metabolism
  • Vasoconstrictor Agents / pharmacology*
  • Vasodilator Agents / pharmacology*

Substances

  • Opioid Peptides
  • Potassium Channels, Inwardly Rectifying
  • Tachykinins
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Capsaicin