Hossen M A, Sugimoto Y, Kayasuga R, Kamei C
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Tsushima-naka 1-1-1, Okayama 700-8530, Japan.
Br J Dermatol. 2003 Jul;149(1):17-22. doi: 10.1046/j.1365-2133.2003.05341.x.
Although the roles of histamine H3 receptors have been studied in several tissues such as the brain, lung, spleen, colon and peripheral sensory nerve endings, the involvement of H3 receptors in skin responses particularly in relation to scratching behaviour are not well documented.
This work was performed to study the effects of histamine H3 antagonists on scratching behaviour in mast cell-deficient mice.
Histamine H3 antagonists iodophenpropit and clobenpropit, histamine and substance P were injected intradermally into the rostral part of the back of mast cell-deficient (WBB6F1 W/Wv) and wild-type (WBB6F1+/+) mice and scratching behaviour was measured for 60 min. The effects of H1 antagonists on scratching behaviour induced by H3 antagonists were also investigated.
Intradermal injection of iodophenpropit and clobenpropit at doses of 10 and 100 nmol per site caused significant increases in scratching behaviour in both mast cell-deficient and wild-type mice. Histamine also caused a dose-related increase in the incidence of scratching behaviour, and a significant effect was observed at a dose of 100 nmol per site in both mast cell-deficient and wild-type mice. Substance P was also effective in causing scratching behaviour in both mast cell-deficient and wild-type mice. However, histamine H1 antagonists diphenhydramine and chlorphenamine failed to inhibit H3 antagonist-induced scratching behaviour in both types of mice.
Our results indicated that intradermal injection of H3 antagonists induces scratching behaviour and that chemical mediators other than histamine seem to be involved in the response.
尽管组胺H3受体在大脑、肺、脾脏、结肠和外周感觉神经末梢等多种组织中的作用已得到研究，但H3受体在皮肤反应尤其是与搔抓行为相关方面的参与情况尚无充分记录。
本研究旨在探讨组胺H3拮抗剂对肥大细胞缺陷小鼠搔抓行为的影响。
将组胺H3拮抗剂碘苯丙哌啶和氯苯丙哌啶、组胺和P物质皮内注射到肥大细胞缺陷（WBB6F1 W/Wv）和野生型（WBB6F1+/+）小鼠背部的头端部分，并测量60分钟内的搔抓行为。还研究了H1拮抗剂对H3拮抗剂诱导的搔抓行为的影响。
在肥大细胞缺陷小鼠和野生型小鼠中，每部位皮内注射10和100 nmol剂量的碘苯丙哌啶和氯苯丙哌啶均导致搔抓行为显著增加。组胺也引起搔抓行为发生率的剂量相关增加，在肥大细胞缺陷小鼠和野生型小鼠中，每部位100 nmol剂量时均观察到显著效果。P物质在肥大细胞缺陷小鼠和野生型小鼠中也能有效引起搔抓行为。然而，组胺H1拮抗剂苯海拉明和氯苯那敏未能抑制两种类型小鼠中H3拮抗剂诱导的搔抓行为。
我们的结果表明，皮内注射H3拮抗剂可诱导搔抓行为，且除组胺外的其他化学介质似乎参与了该反应。
