Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels
Caffeine activates mouse TRPA1 channels but suppresses human TRPA1 channels
复制标题
DOI：
10.1073/pnas.0809769105
复制
发表时间：
2008-11-11
影响因子：
11.1
通讯作者：
Kubol, Yoshihiro
中科院分区：
文献类型：
--
作者：
Nagatomo, Katsuhiro;Kubol, Yoshihiro
咖啡因具有多种明确的药理作用，但在哺乳动物中，尚不存在已知的由咖啡因激活的质膜受体或离子通道。我们通过 Ca-i(2+) 成像和电生理分析观察到咖啡因激活异源表达系统中的小鼠瞬时受体电位 A1 (TRPA1)。这些对咖啡因的反应在 WT 小鼠的急性分离的背根神经节感觉神经元中得到了证实，这些神经元已知表达 TRPA1，但在 TRPA1 KO 小鼠的神经元中没有观察到。通过免疫组织化学方法检测小鼠舌神经纤维和神经束中 TRPA1 的表达。此外，WT 小鼠（而非 KO 小鼠）表现出对含咖啡因水的明显厌恶。这些结果表明，在感觉神经元中表达的小鼠 TRPA1 通道会导致人们厌恶饮用含咖啡因的水，这表明它们介导了对咖啡因的感知。最后，我们观察到咖啡因不会激活人类TRPA1；相反，它会抑制其活动。
Caffeine has various well-characterized pharmacological effects, but in mammals there are no known plasma membrane receptors or ion channels activated by caffeine. We observed that caffeine activates mouse transient receptor potential A1 (TRPA1) in heterologous expression systems by Ca-i(2+) imaging and electrophysiological analyses. These responses to caffeine were confirmed in acutely dissociated dorsal root ganglion sensory neurons from WT mice, which are known to express TRPA1, but were not seen in neurons from TRPA1 KO mice. Expression of TRPA1 was detected immunohistochemically in nerve fibers and bundles in the mouse tongue. Moreover, WT mice, but not KO mice, showed a remarkable aversion to caffeine-containing water. These results demonstrate that mouse TRPA1 channels expressed in sensory neurons cause an aversion to drinking caffeine-containing water, suggesting they mediate the perception of caffeine. Finally, we observed that caffeine does not activate human TRPA1; instead, it suppresses its activity.