Fischer A, Forssmann W G, Undem B J
Institute for Anatomy and Cell Biology, Justus-Liebig-University, Giessen, Germany.
J Pharmacol Exp Ther. 1998 May;285(2):902-7.
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.
痛敏肽是阿片肽家族中的一种新型神经肽，最近被确定为类阿片受体样“孤儿”受体的内源性配体。与其他阿片类药物不同，痛敏肽在体内具有痛觉过敏作用。在本研究中，发现痛敏肽可抑制电场刺激诱导的豚鼠离体支气管制剂的速激肽能收缩。阈值效应约为1 nM，在0.1 μM时，痛敏肽抑制5 Hz刺激诱发的收缩超过50%。发现这种抑制作用是由一种节前机制介导的，该机制不涉及任何经典的（μ、δ和κ）阿片受体。尽管痛敏肽的作用继发于类阿片受体样刺激这一假说无法通过药理学方法解决，但在迷走神经上感觉神经节中发现了类阿片受体样受体mRNA的表达，含速激肽的感觉神经元的细胞体位于该神经节中。气道壁中与含速激肽纤维不同的痛敏肽免疫反应性神经纤维被确定为痛敏肽的内源性来源。这些数据表明，痛敏肽可能通过调节速激肽能神经传递来影响气道生理功能。
