title: Thromboxane A2 is Involved in Itch-associated Responses in Mice with Atopic Dermatitis-like Skin Lesions.
abstract: To investigate the mechanisms underlying itching in atopic dermatitis, we examined whether thromboxane (TX) A2, an arachidonic acid metabolite, is involved in spontaneous scratching, an itch-related response, in NC mice with atopic dermatitis-like skin lesions. The TXA2 receptor (TP) antagonist ONO-3708 inhibited the spontaneous scratching. The mRNA expression of TX synthase (TXSyn) distributed mainly in epidermis and the concentration of TXB2, a metabolite of TXA2, were increased in lesional skin. Scratching caused by the PAR2 agonist SLIGRL-NH2 was suppressed by ONO-3708. SLIGRL-NH2-induced scratching decreased approximately 75% in TP-deficient mice, compared to wild-type mice. In primary cultures of mouse keratinocytes, SLIGRL-NH2 induced the production of TXA2, as evidenced by the increased TXB2, which was inhibited by the TXSyn inhibitor sodium ozagrel and a PAR2-neutralizing antibody. Taken together, these results suggest that epidermal TXA2, which may be produced via PAR2 activation, is involved in itching in atopic dermatitis.
authors.affiliation: Department of Applied Pharmacology, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Toyama, Japan. andoht@pha.u-toyama.ac.jp.
authors.forename: Tsugunobu
authors.initials: T
authors.lastname: Andoh
authors.forename: Ai
authors.initials: A
authors.lastname: Yamamoto
authors.forename: Satomi
authors.initials: S
authors.lastname: Haza
authors.forename: Koh-Ichi
authors.initials: KI
authors.lastname: Yuhki
authors.forename: Fumitaka
authors.initials: F
authors.lastname: Ushikubi
authors.forename: Shu
authors.initials: S
authors.lastname: Narumiya
authors.forename: Yasushi
authors.initials: Y
authors.lastname: Kuraishi
mesh_terms: D000818:Animals; D003876:Dermatitis, Atopic / Q000188:drug therapy* / Q000378:metabolism*; D015603:Keratinocytes / Q000378:metabolism; D008297:Male; D008689:Methacrylates / Q000494:pharmacology; D051379:Mice; D009842:Oligopeptides / Q000009:adverse effects / Q000494:pharmacology; D011537:Pruritus / Q000188:drug therapy* / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D044464:Receptor, PAR-2 / Q000037:antagonists & inhibitors; D013928:Thromboxane A2 / Q000031:analogs & derivatives* / Q000378:metabolism* / Q000494:pharmacology
chemical_list: D008689:Methacrylates; D009842:Oligopeptides; D012333:RNA, Messenger; D044464:Receptor, PAR-2; C112356:seryl-leucyl-isoleucyl-glycyl--arginyl-leucinamide; D013928:Thromboxane A2; C049855:ONO 3708; C034364:ozagrel