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Journal of Pharmacology and Experimental Therapeutics

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OtherPULMONARY PHARMACOLOGY

Nociceptin-Induced Inhibition of Tachykinergic Neurotransmission in Guinea Pig Bronchus ,

Axel Fischer, Wolf-Georg Forssmann and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics May 1998, 285 (2) 902-907;
Axel Fischer
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Wolf-Georg Forssmann
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Bradley J. Undem
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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

  • Send reprint requests to: Axel Fischer, Institut für Anatomie und Zellbiologie, Justus-Liebig-Universität, Aulweg 123, 35385 Giessen, Germany.

  • ↵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.

  • ↵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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Journal of Pharmacology and Experimental Therapeutics
Vol. 285, Issue 2
1 May 1998
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OtherPULMONARY PHARMACOLOGY

Nociceptin-Induced Inhibition of Tachykinergic Neurotransmission in Guinea Pig Bronchus ,

Axel Fischer, Wolf-Georg Forssmann and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 902-907;

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OtherPULMONARY PHARMACOLOGY

Nociceptin-Induced Inhibition of Tachykinergic Neurotransmission in Guinea Pig Bronchus ,

Axel Fischer, Wolf-Georg Forssmann and Bradley J. Undem
Journal of Pharmacology and Experimental Therapeutics May 1, 1998, 285 (2) 902-907;
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  • Inhibition of 5-Lipoxygenase Diminishes Neurally Evoked Tachykinergic Contraction of Guinea Pig Isolated Airway
  • Dehydroepiandrosterone and Analogs Inhibit DNA Binding of AP-1 and Airway Smooth Muscle Proliferation
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