Nociceptin-induced inhibition of tachykinergic neurotransmission in guinea pig bronchus.
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 microM, 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 (mu, delta and kappa) 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.
Fischer
A
A
Institute for Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
Forssmann
W G
WG
Undem
B J
BJ
D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation; D002211:Capsaicin / Q000494:pharmacology; D004558:Electric Stimulation; D006168:Guinea Pigs; D007150:Immunohistochemistry; D008297:Male; D009119:Muscle Contraction; D018847:Opioid Peptides / Q000494:pharmacology*; D016133:Polymerase Chain Reaction; D011957:Receptors, Opioid / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects*; D015320:Tachykinins / Q000502:physiology*; D000097629:Nociceptin
D002211:Capsaicin; D018847:Opioid Peptides; D011957:Receptors, Opioid; D015320:Tachykinins; D000097629:Nociceptin