Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus

Axel Fischer, Wolf Georg Forssmann, Bradley J. Undem

Research output: Contribution to journalArticlepeer-review

Abstract

Nociceptin is a novel neuropeptide of the opioid peptide family recently identified as the endogenous ligand of the opioid receptor-like 'orphan' receptor. Unlike other opioids, nociceptin has hyperalgesic effects in vivo. In the present study, nociceptin was found to inhibit electrical field stimulation-induced tachykinergic contractions of the guinea pig isolated bronchus preparation. The threshold effect was about 1 nM, and at 0.1 μM, nociceptin inhibited contractions evoked by 5-Hz stimulation by more than 50%. This inhibitory effect was found to be mediated by a prejunctional mechanism involving none of the classical (μ, δ and κ) opioid receptors. Although the hypothesis that the effect of nociceptin was secondary to opioid receptor-like stimulation cannot be pharmacologically addressed, opioid receptor-like-receptor-mRNA was found to be expressed in the upper vagal sensory ganglion, where the cell bodies of the tachykinin-containing sensory neurons are located. Nociceptin immunoreactive nerve fibers in the airway wall, distinct from the tachykinin-containing fibers, were identified as an endogenous source of nociceptin. These data indicate that noniceptin may influence airway physiology by modulating tachykinergic neurotransmission.

Original languageEnglish (US)
Pages (from-to)902-907
Number of pages6
JournalJournal of Pharmacology and Experimental Therapeutics
Volume285
Issue number2
StatePublished - Jun 4 1998

ASJC Scopus subject areas

  • Molecular Medicine
  • Pharmacology

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