Thromboxane A2 induces itch-associated responses through TP receptors in the skin in mice
Thromboxane A2 induces itch-associated responses through TP receptors in the skin in mice
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DOI：
10.1038/sj.jid.5700810
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发表时间：
2007-08-01
影响因子：
6.5
通讯作者：
Kuraishi, Yasushi
中科院分区：
文献类型：
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作者：
Andoh, Tsugunobu;Nishikawa, Yumi;Kuraishi, Yasushi
血栓烷A（2）（TXA（2））是花生四烯酸的代谢产物，由环氧合酶和血栓烷合酶产生，被认为参与慢性皮炎。本研究调查了TXA（2）在皮肤瘙痒中的作用。皮内注射U-46619（一种稳定的TXA类似物）（2）可引起小鼠抓挠，这是一种瘙痒相关反应。剂量-反应曲线呈钟形，在每个部位10 nmol时具有最大效应。U-46619的作用被TP拮抗剂ONO-3708抑制，TP受体缺乏则被取消。TP受体主要表达于皮肤的神经纤维和角质形成细胞。血栓素合酶也在角质形成细胞中表达。U-46619增加背根神经节神经元和角质形成细胞的原代培养物中的细胞内Ca 2+离子浓度。结果表明，角质形成细胞合成的TXA（2）作为瘙痒介质。它可能通过激活初级传入神经和角质形成细胞上的TP受体引起瘙痒;角质形成细胞可能产生瘙痒介质，包括TXA（2）。因此，血栓素合酶抑制剂和TP受体拮抗剂将成为抗血栓药物的候选药物。
Thromboxane A(2) (TXA(2)), a metabolite of arachidonic acid produced by cyclooxygenase and thromboxane synthase, is thought to participate in chronic dermatitis. This study investigated the involvement of TXA(2) in cutaneous itch. An intradermal injection of U-46619, a stable analogue of TXA(2), elicited scratching, an itchassociated response, in mice. Dose-response curve was bell shaped with a maximum effect at 10 nmol per site. The action of U-46619 was inhibited by a coinjection of the TP antagonist ONO-3708 and was abolished by TP receptor deficiency. TP receptor was mainly expressed in nerve fiber in the skin and keratinocytes. Thromboxane synthase was also expressed in keratinocytes. U-46619 increased intracellular Ca2+ ion concentration in primary cultures of dorsal root ganglion neurons and keratinocytes. The results suggest that TXA(2) synthesized by keratinocytes acts as an itch mediator. It may elicit itch through the activation of TP receptors on primary afferents and keratinocytes; keratinocytes may produce itch mediators including TXA(2). Thus, thromboxane synthase inhibitor and TP receptor antagonists will be candidates for antipruritic medicines.