INHIBITION OF NOCICEPTIN ON SENSORY NEUROPEPTIDE RELEASE AND MAST CELL-MEDIATED PLASMA EXTRAVASATION IN RATS

Nociceptin (20 mu g/kg i.p.) strongly inhibited cutaneous Evans blue a ccumulation in the chronically denervated hindpaw of the rat in respon se to mast cell degranulating peptide (MCDP, 0.25 mu g in 100 mu l) bu t it had no and marginal effect on plasma extravasation induced by 5-h ydroxytryptamine (5-HT, 0.5 mu g in 100 mu l) and histamine (0.1 mu g in 100 mu 1), respectively. Release of sensory neuropeptides such as s ubstance P, calcitonin gene-related peptide (CGRP) and somatostatin fr om the rat isolated trachea in response to capsaicin (10(-8) M) or bra dykinin (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 b oth inhibited by nociceptin that participates in the anti-inflammatory effect of the peptide. (C) 1998 Elsevier Science B.V.