Cardiovascular and Respiratory Studies, The University of Hull, HU6 7RX, UK.
The Procter & Gamble Company, Mason, OH 45040, USA.
Cells. 2014 Jun 11;3(2):616-26. doi: 10.3390/cells3020616.
Transient receptor potential (TRP) ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1) receptors are implicated in modulation of cough and nociception. In vivo, TRPA1 and TRPV1 are often co-expressed in neurons and TRPA1V1 hetero-tetramer formation is noted in cells co-transfected with the respective expression plasmids. In order to understand the impact of TRP receptor interaction on activity, we created stable cell lines expressing the TRPA1, TRPV1 and co-expressing the TRPA1 and TRPV1 (TRPA1V1) receptors. Among the 600 compounds screened against these receptors, we observed a number of compounds that activated the TRPA1, TRPV1 and TRPA1V1 receptors; compounds that activated TRPA1 and TRPA1V1; compounds that activated TRPV1 and TRPA1V1; compounds in which TRPA1V1 response was modulated by either TRPA1 or TRPV1; and compounds that activated only TRPV1 or TRPA1 or TRPA1V1; and one compound that activated TRPA1 and TRPV1, but not TRPA1V1. These results suggest that co-expression of TRPA1 and TRPV1 receptors imparts unique activation profiles different from that of cells expressing only TRPA1 or TRPV1.
瞬时受体电位 (TRP) 锚蛋白 1 (TRPA1) 和香草素 1 (TRPV1) 受体被认为参与了咳嗽和痛觉的调节。在体内,TRPA1 和 TRPV1 通常在神经元中共同表达,并且在共转染相应表达质粒的细胞中观察到 TRPA1V1 异四聚体的形成。为了了解 TRP 受体相互作用对活性的影响,我们创建了稳定表达 TRPA1、TRPV1 并共表达 TRPA1 和 TRPV1(TRPA1V1)受体的细胞系。在针对这些受体筛选的 600 种化合物中,我们观察到一些化合物激活了 TRPA1、TRPV1 和 TRPA1V1 受体;激活 TRPA1 和 TRPA1V1 的化合物;激活 TRPV1 和 TRPA1V1 的化合物;TRPA1V1 反应受 TRPA1 或 TRPV1 调节的化合物;以及仅激活 TRPV1 或 TRPA1 或 TRPA1V1 的化合物;一种化合物激活 TRPA1 和 TRPV1,但不激活 TRPA1V1。这些结果表明,TRPA1 和 TRPV1 受体的共表达赋予了不同于仅表达 TRPA1 或 TRPV1 的细胞的独特激活谱。