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 nociceptin may influence airway physiology by modulating tachykinergic neurotransmission.
Footnotes
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Send reprint requests to: Axel Fischer, Institut für Anatomie und Zellbiologie, Justus-Liebig-Universität, Aulweg 123, 35385 Giessen, Germany.
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↵1 Part of this work has been previously presented in abstract form: Undem BJ, Meeker SA, and Fischer A (1997) Am. J. Respir. Crit. Care Med. 155:A484.
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↵2 This study was funded in part by a joint program of the National Institutes of Health, Bethesda, Maryland, and the Bundesministerium fur Bildung und Forschung, Bonn, Germany.
- Abbreviations:
- ORL1
- opioid receptor-like
- EFS
- electrical field stimulation
- NK
- neurokinin
- PBS
- phosphate-buffered saline, PNS, peripheral nervous system, TTX, tetrodotoxin, RT-PCR, reverse transcription polymerase chain reaction
- dNTP
- desoxynucleotide triphosphate
- Received September 15, 1997.
- Accepted December 22, 1997.
- The American Society for Pharmacology and Experimental Therapeutics
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