描述鼠标cold-menthol受体TRPM8 VR1使用草酸受体1型荧光成像板读者(FLIPR)测定。

文章的细节

引用

复制到剪贴板

贝伦特HJ Germann T, Gillen C, Hatt H, Jostock R

描述鼠标cold-menthol受体TRPM8 VR1使用草酸受体1型荧光成像板读者(FLIPR)测定。

Br J杂志。2004年2月,141 (4):737 - 45。Epub 2004 2月2。

PubMed ID

14757700 (在PubMed

]

文摘

1。TRPM8 (CMR1)是一个Ca(2 +)透水通道,可以激活温度低、薄荷醇、桉油精和icilin。它属于瞬时受体电位(TRP)的家庭,因此与草酸受体1型(VR1 TRPV1)。我们测试是否物质结构与薄荷醇,或产生一个冷却的感觉,可以激活TRPM8,相比TRPM8和VR1这些配体的反应。2。70两种气味和menthol-related物质重组的影响鼠标TRPM8 (mTRPM8),在HEK293细胞中表达,使用FLIPR化验检查。总之,10物质(芳樟醇、香叶醇、羟基香予醛WS-3, WS-23, FrescolatMGA, FrescolatML, PMD38, CoolactP和冷却剂10)受体激动剂被发现。3所示。受体激动剂的EC(50)值定义它们的相对效能:icilin (0.2 + / - -0.1 microM) > FrescolatML (3.3 + / - -1.5 microM) > WS-3 (3.7 + / - -1.7 microM) >(-)薄荷醇(4.1 + / - -1.3 microM) > frescolatMAG (4.8 + / - -1.1 microM) >冷却剂10 (6 + / -2.2 microM) >(+)薄荷醇(14.4 + / - -1.3 microM) > PMD38 (31 + / -1.1 microM) > WS-23 (44 + / -7.3 microM) > Coolact P (66 + / -20 microM) >香叶醇(5.9 + / - -1.6毫米)>芳樟醇(6.7 + / - -2.0毫米)>桉油精(7.7 + / - -2.0毫米)>羟基香予醛(19.6 + / - -2.2毫米)。4所示。 Known VR1 antagonists (BCTC, thio-BCTC and capsazepine) were also able to block the response of TRPM8 to menthol (IC(50): 0.8+/-1.0, 3.5+/-1.1 and 18+/-1.1 microM, respectively). 5. The Ca(2+) response of hVR1-transfected HEK293 cells to the endogenous VR1 agonist N-arachidonoyl-dopamine was potentiated by low pH. In contrast, menthol- and icilin-activated TRPM8 currents were suppressed by low pH. 6. In conclusion, in the present study, we identified 10 new agonists and three antagonists of TRPM8. We found that, in contrast to VR1, TRPM8 is inhibited rather than potentiated by protons.

DrugBank数据引用了这篇文章

药物靶点

药物	目标	类	生物	药理作用	行动
Levomenthol	瞬时受体电位阳离子通道亚科8 M成员	蛋白质	人类	是的	诱导物	细节