4-Methylhistamine dihydrochloride

4-Methylhistamine dihydrochloride（4-Methylhistamine dihydrochloride）是H4受体的选择性激动剂，pEC50值为7.4 ± 0.1（α= 1）[1]。

组胺H4受体（H4R）参与了肥大细胞的化学趋向性以及白细胞的炎症定位[1]。

在转染的细胞中，相对于结合其它组胺受体，4-Methylhistamine dihydrochloride与hH4R结合具有最高的亲和力。4-Methylhistamine dihydrochloride和hH4R之间的相互作用具有较高的选择性，分别是H3R和H2R的100倍以上，是H1R 的100,000倍以上。尽管4-Methylhistamine dihydrochloride对hH4R的亲和力比较低，但它对大鼠和小鼠H4R具有高亲和性，Ki值分别为73和55 nM。JNJ 7777120可以拮抗4-Methylhistamine dihydrochloride对hH4R的激动作用。作为一个完整的H4激动剂，4-Methylhistamine dihydrochloride对大鼠和小鼠H4R的pEC50值分别为5.6 ± 0.1和5.8 ± 0.1[1]。

被禁食18小时后，给予大鼠腹膜内注射单剂量的4-Methylhistamine dihydrochloride。2小时后，关节内注射LPS。经过4-Methylhistamine dihydrochloride和LPS单独处理的两组中TNF-α和NF-κB的表达分别增加，滑液和全血中IKB-α水平下降。此外，IL-1β、TNF-α和NF-κB的mRNA水平显著增加。蛋白质印迹分析结果也证实，经4-Methylhistamine dihydrochloride和LPS处理的组中TNF-α、JAK-1、NF-κB和STAT-3的表达增加。JNJ 7777120完全抑制了膝盖发炎组织中这些物质的增加[2]。

参考文献：
[1].  Lim HD, van Rijn RM, Ling P, et al. Evaluation of histamine H1-, H2-, and H3-receptor ligands at the human histamine H4 receptor: identification of 4-methylhistamine as the first potent and selective H4 receptor agonist. Journal of Pharmacology and Experimental Therapeutics, 2005, 314(3): 1310-1321.
[2].  Ahmad SF, Ansari MA, Zoheir KMA, et al. Regulation of TNF-α and NF-κB activation through the JAK/STAT signaling pathway downstream of histamine 4 receptor in a rat model of LPS-induced joint inflammation. Immunobiology, 2015, 220(7): 889-898.