Nociceptin/orphanin FQ inhibits electrically induced contractions of the human bronchus via NOP receptor activation

Peptides. 2005 Aug;26(8):1492-6. doi: 10.1016/j.peptides.2005.03.016. Epub 2005 Apr 18.

Abstract

Nociceptin/orphanin FQ (N/OFQ) has been reported to inhibit neurogenic contractions in various tissues, including guinea pig airways. In the present study, we investigated the ability of N/OFQ to affect cholinergic contractions of human bronchi elicited by electrical field stimulation (EFS). Tissues were obtained from 23 patients undergoing surgery for lung cancer. EFS (20 Hz, 320 mA, 1.5 ms, 10 s) was applied five times every 20 min. Contractions induced by EFS were abolished by either TTX (1 microM) or atropine (1 microM) and concentration-dependently (10 nM-1 microM) inhibited by N/OFQ (Emax, 11.5+/-1.8% inhibition). The inhibitory effects of N/OFQ were mimicked by the N/OFQ receptor (NOP) ligand [Arg14, Lys15]N/OFQ which displayed however, higher significant maximal effects (17.7+/-2.9% inhibition, P<0.05). The actions of N/OFQ and [Arg14, Lys15]N/OFQ were not affected by naloxone (1 microM) while prevented by the selective NOP receptor antagonist UFP-101 (10 microM). Moreover, the inhibitory effects of NOP agonists were no longer evident in tissues treated with tertiapin (10 microM), an inhibitor of inward-rectifier potassium channels. In conclusion, the present data demonstrate that N/OFQ inhibited acetylcholine (ACh) release in the human bronchi via NOP receptor activation. This effect may involve stimulation of potassium currents.

MeSH terms

  • Aged
  • Bronchi / drug effects
  • Bronchi / physiology*
  • Electric Stimulation*
  • Humans
  • Middle Aged
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology*
  • Opioid Peptides / pharmacology*
  • Peptide Fragments / pharmacology*
  • Receptors, Opioid / drug effects
  • Receptors, Opioid / metabolism*

Substances

  • Opioid Peptides
  • Peptide Fragments
  • Receptors, Opioid
  • nociceptin
  • nociceptin receptor