Inhibition of nociceptin on sensory neuropeptide release and mast cell-mediated plasma extravasation in rats.

Nociceptin (20 microg/kg i.p.) strongly inhibited cutaneous Evans blue accumulation in the chronically denervated hindpaw of the rat in response to mast cell degranulating peptide (MCDP, 0.25 microg in 100 microl) but it had no and marginal effect on plasma extravasation induced by 5-hydroxytryptamine (5-HT, 0.5 microg in 100 microl) and histamine (0.1 microg in 100 microl), respectively. Release of sensory neuropeptides such as substance P, calcitonin gene-related peptide (CGRP) and somatostatin from the rat isolated trachea in response to capsaicin (10(-8) M) or bradykinin (10(-7) M) were also attenuated by nociceptin (100 and 300 nM). It is concluded that chemically induced discharge of mediators from mast cells and from capsaicin-sensitive afferent nerve terminals are both inhibited by nociceptin that participates in the anti-inflammatory effect of the peptide.