Vol. 285, Issue 2, 902-907, May 1998

Nociceptin-Induced Inhibition of Tachykinergic Neurotransmission in Guinea Pig Bronchus

Axel Fischer, Wolf-Georg Forssmann and Bradley J. Undem

Institute for Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany (A.F.); Lower Saxony Institute for Peptide Research, Hannover, Germany (W.G.F.) and The Johns Hopkins Asthma and Allergy Center (B.J.U.), Baltimore, Maryland

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,  and ) 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.