Intradermal nociceptin elicits itch-associated responses through leukotriene B4 in mice

JOURNAL OF INVESTIGATIVE DERMATOLOGY

卷:123

Article

Andoh, T ; Yageta, Y ; Takeshima, H ; Kuraishi, Y

关键词: itch;    keratinocyte;    leukotriene B-4;    nociceptin;    ORL1 receptor;    scratching;   

DOI  :  10.1111/j.0022-202X.2004.22704.x

来源: Elsevier

【 摘 要 】

Nociceptin, the endogenous peptide ligand for opioid receptor like-1 (ORL1) receptor, has been implicated in the inflammation and pain in the skin. We examined whether nociceptin is a pruritogen in mice. Intradermal injections of nociceptin (1-100 nmol per site) concentration dependently increased scratching in ICR mice; the effect started within 1 min, peaked at 10-20 min, and almost subsided by 30 min. The nociceptin action was absent in ORL1 receptor-deficient (ORL1(-/-)) mice. Systemic, but not local, treatment with naloxone significantly inhibited scratching induced by nociceptin. The action of nociceptin was inhibited by the leukotriene B-4 receptor antagonist ONO-4057 and azelastine, which inhibits the action and production of leukotriene B-4 in the skin. Prepronociceptin and ORL1 receptor mRNAs were substantially expressed in the skin, whereas their expression levels were very low in the dorsal root ganglia. In the skin, nociceptin- and ORL1 receptor-like immunoreactivities were localized in the epidermis. Administration of nociceptin to primary cultures of keratinocytes from ICR and C57BL/6 (ORL1(+/+)) mice, but not ORL1(-/-) mice, produced leukotriene B-4. The results suggest that nociceptin acts on ORL1 receptor on the keratinocytes to produce leukotriene B-4, which induces itch-associated responses in mice.

【 授权许可】

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