Intradermal application of nociceptin increases vascular permeability in rats: the possible involvement of histamine release from mast cells.

Intradermal application of nociceptin was used to investigate its in vivo effect on the inflammatory response in rats. Intradermal nociceptin (5 pmol/site-5 nmol/site) increased vascular permeability in a dose-dependent manner. The increased vascular permeability by nociceptin (5 nmol/site) was dose-dependently inhibited by the histamine H1 receptor antagonist pyrilamine (50 pmol/site-5 nmol/site). In rat peritoneal mast-cell preparation, nociceptin (10(-8)-10(-4) M) dose-dependently stimulated histamine release. The effect of nociceptin (10(-5) M) occurred rapidly (within 30 s) and was inhibited by pertussis toxin, Ca2+, but was not sensitive to naloxone, a classical opioid receptor antagonist. These characteristics are in agreement with features of the opioid-receptor-like 1 (ORL1) receptor, a non-classical opioid receptor linked to a pertussis toxin-sensitive G protein. Taken together, these data suggest that nociceptin, likely acting via the ORL1 receptor at the site of inflammation, might be critical for the enhancement of the inflammatory response by stimulating histamine release from mast cells.