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组胺H4受体在小鼠过敏性结膜炎中的作用

Role of histamine H(4) receptor in allergic conjunctivitis in mice.

作者信息

Nakano Yoshiyuki, Takahashi Yuji, Ono Rie, Kurata Yasunori, Kagawa Yoto, Kamei Chiaki

机构信息

Department of Medicinal Pharmacology, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama, Japan.

出版信息

Eur J Pharmacol. 2009 Apr 17;608(1-3):71-5. doi: 10.1016/j.ejphar.2009.02.035. Epub 2009 Feb 26.

Abstract

We investigated the character of histamine H(1) receptor and H(4) receptor in allergic conjunctivitis. Histamine is the most important mediator in allergic conjunctivitis. We measured eye scratching behavior and allergic-like symptoms score, that is, hyperemia and edema in ICR mice, and examined which receptors intimately involved in allergic conjunctivitis. Histamine caused a dose-dependent eye scratching behavior and allergic-like symptoms. Histamine H(1) receptor antagonist (levocabastine) and H(4) receptor antagonist (JNJ7777120) inhibited eye scratching behavior and histamine H(1) receptor antagonist inhibited allergic-like symptoms induced by histamine. Additionally, combination of levocabastine and JNJ7777120 caused more potent inhibition in allergic conjunctivitis. On the other hand, both selective histamine H(1) receptor agonist (HTMT) and selective H(4) receptor agonist (4-methylhistamine) induced a dose-dependent eye scratching behavior and allergic-like symptoms. JNJ7777120 inhibited the effect of HTMT. However, levocabastine caused no inhibition on the response of 4-methylhistamine. H(4) receptor was closely related with allergic conjunctivitis. H(4) receptor antagonists may be effective in allergic conjunctivitis which showed no inhibition by histamine H(1) receptor antagonists.

摘要

我们研究了变应性结膜炎中组胺H(1)受体和H(4)受体的特性。组胺是变应性结膜炎中最重要的介质。我们测量了ICR小鼠的眼部搔抓行为和类过敏症状评分,即充血和水肿,并研究了哪些受体与变应性结膜炎密切相关。组胺引起剂量依赖性的眼部搔抓行为和类过敏症状。组胺H(1)受体拮抗剂(左卡巴斯汀)和H(4)受体拮抗剂(JNJ7777120)抑制眼部搔抓行为,组胺H(1)受体拮抗剂抑制组胺诱导的类过敏症状。此外,左卡巴斯汀和JNJ7777120联合使用对变应性结膜炎的抑制作用更强。另一方面,选择性组胺H(1)受体激动剂(HTMT)和选择性H(4)受体激动剂(4-甲基组胺)均诱导剂量依赖性的眼部搔抓行为和类过敏症状。JNJ7777120抑制HTMT的作用。然而,左卡巴斯汀对4-甲基组胺的反应没有抑制作用。H(4)受体与变应性结膜炎密切相关。H(4)受体拮抗剂可能对组胺H(1)受体拮抗剂无抑制作用的变应性结膜炎有效。

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