TY - JOUR
T1 - Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus
AU - Fischer, Axel
AU - Forssmann, Wolf Georg
AU - Undem, Bradley J.
PY - 1998/6/4
Y1 - 1998/6/4
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0031808880&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0031808880&partnerID=8YFLogxK
M3 - Article
C2 - 9580642
AN - SCOPUS:0031808880
SN - 0022-3565
VL - 285
SP - 902
EP - 907
JO - Journal of Pharmacology and Experimental Therapeutics
JF - Journal of Pharmacology and Experimental Therapeutics
IS - 2
ER -