Pinacidil, a Katp channel opener, identified as a novel agonist for TRPA1
Pinacidil, a Katp channel opener, identified as a novel agonist for TRPA1
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Pinacidil 是一种 Katp 通道开放剂，被确定为 TRPA1 的新型激动剂
DOI：
10.1007/s11434-012-5035-0
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发表时间：
2012-03
影响因子：
--
通讯作者：
Jianfeng Liu
中科院分区：
文献类型：
--
作者：
Lianghui Ma;Ying Deng;Bi Zhang;Yanqiu Bai;Jing Cao;Shiyou Li;Jianfeng Liu
瞬时受体电位锚蛋白1（TRPA 1）阳离子通道被各种刺激性和刺激性化合物激活，并且它也介导对有害寒冷的感知。识别该通道的不同激动剂对于理解其激活机制是重要的。因此，使用激动剂诱导的钙内流测定进行新型TRPA 1激动剂的筛选。在筛选的90种化合物中，吡那地尔被鉴定为该通道的新型激动剂。吡那地尔是已知的Katp通道开放剂，其EC 50值为1-3 μmol/L。相比之下，吡那地尔对TRPA 1的EC 50值相对较高（260 μmol/L）。重组HEK-TRPA 1细胞对另一种Katp通道开放剂P1075没有反应，表明吡那地尔对TRPA 1的作用是高度特异性的。进一步的研究表明，吡那地尔的激动剂活性可以被TRP通道抑制剂钌红和HC-030031阻断。使用谷胱甘肽（GSH）和定点突变，我们证明了吡那地尔可以激活TRPA 1的N-末端的关键氨基酸C619，C639和C663的共价修饰。
The transient receptor potential Ankyrin 1 (TRPA1) cation channel is activated by various pungent and irritant compounds, and it also mediates the perception of noxious cold. Identification of different agonists for this channel is important for understanding its activation mechanism. Therefore, a screen for novel TRPA1 agonists was performed using an agonist-induced calcium influx assay. Out of 90 compounds screened, pinacidil was identified as a novel agonist for this channel. Pinacidil is a known opener of the Katp channel, for which it has an EC50 value of 1–3 μmol/L. In comparison, the EC50 value of pinacidil for TRPA1 is relatively high (260 μmol/L). Recombinant HEK-TRPA1 cells did not respond to P1075, another Katp channel opener, suggesting that the effect of pinacidil on TRPA1 was highly specific. Further studies revealed that the agonist activity of pinacidil could be blocked by the TRP channel inhibitors, ruthenium red and HC-030031. Using glutathione (GSH) and site-specific mutagenesis, we demonstrated that pinacidil could activate TRPA1 by covalent modification of the critical amino acids C619, C639 and C663 in the N-terminus of TRPA1.
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影响因子：
3
作者：
L. Gojković-Bukarica;B. Beleslin-Čokić;A. Novaković;M. Perić;J. Marković-Lipkovski;S. Ćirović;D. Nežić;A. Lešić;V. Kanjuh;H. Heinle
通讯作者：
L. Gojković-Bukarica;B. Beleslin-Čokić;A. Novaković;M. Perić;J. Marković-Lipkovski;S. Ćirović;D. Nežić;A. Lešić;V. Kanjuh;H. Heinle
影响因子：
3.3
作者：
Cavanaugh, E. J.;Simkin, D.;Kim, D.
通讯作者：
Kim, D.
影响因子：
16.2
作者：
Kwan, KY;Allchorne, AJ;Corey, DP
通讯作者：
Corey, DP
影响因子：
--
作者：
B. Sterndorff;P. Johansen
通讯作者：
B. Sterndorff;P. Johansen
影响因子：
5.3
作者：
Nagata, K;Duggan, A;García-Añoveros, J
通讯作者：
García-Añoveros, J