title: Intradermal application of nociceptin increases vascular permeability in rats: the possible involvement of histamine release from mast cells.
abstract: 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.
authors.affiliation: Second Department of Internal Medicine, Nagoya University School of Medicine, 65 Tsuruma-Cho, Showa-Ku, Nagoya 466-8550, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Kimura
authors.forename: K
authors.initials: K
authors.lastname: Kitaichi
authors.forename: K
authors.initials: K
authors.lastname: Hiramatsu
authors.forename: M
authors.initials: M
authors.lastname: Yoshida
authors.forename: Y
authors.initials: Y
authors.lastname: Ito
authors.forename: H
authors.initials: H
authors.lastname: Kume
authors.forename: K
authors.initials: K
authors.lastname: Yamaki
authors.forename: R
authors.initials: R
authors.lastname: Suzuki
authors.forename: K
authors.initials: K
authors.lastname: Takagi
mesh_terms: D000279:Administration, Cutaneous; D000818:Animals; D002118:Calcium / Q000494:pharmacology; D002199:Capillary Permeability / Q000187:drug effects* / Q000502:physiology; D006634:Histamine H1 Antagonists / Q000494:pharmacology; D006636:Histamine Release / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008407:Mast Cells / Q000187:drug effects* / Q000378:metabolism; D018847:Opioid Peptides / Q000494:pharmacology*; D037342:Pertussis Toxin; D011738:Pyrilamine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D011957:Receptors, Opioid / Q000819:agonists*; D010566:Virulence Factors, Bordetella / Q000494:pharmacology; D000094942:Nociceptin Receptor; D000097629:Nociceptin
chemical_list: D002118:Calcium; D006634:Histamine H1 Antagonists; D018847:Opioid Peptides; D037342:Pertussis Toxin; D011738:Pyrilamine; D011957:Receptors, Opioid; D010566:Virulence Factors, Bordetella; D000094942:Nociceptin Receptor; D000097629:Nociceptin; C000722285:Oprl1 protein, rat