Transient receptor potential V2 expressed in sensory neurons is activated by probenecid
Transient receptor potential V2 expressed in sensory neurons is activated by probenecid
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DOI：
10.1016/j.neulet.2007.08.035
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发表时间：
2007-09-25
影响因子：
2.5
通讯作者：
Hwang, Sun Wook
中科院分区：
文献类型：
--
作者：
Bang, Sangsu;Kim, Kyung Yoon;Hwang, Sun Wook
温度激活的瞬时受体电位离子通道（thermoTRPs）被认为具有环境温度传感器的功能，也参与外周疼痛感觉。热trps被多种化学物质激活，其中特定的激活剂已被用于探索特定通道和感觉神经亚型的生理学。使用辣椒素治疗TRPV1是伤害感受器研究的一个典型案例。相比之下，另一种香草蛋白亚型通道TRPV2的特异性药物一直缺乏。在这里，我们通过电生理和钙成像技术在表达TRPV2的HEK293T细胞中证明了probenecid能够激活TRPV2。另外5种感觉热trps - trpv1、TRPV3、TRPV4、TRPM8和trpa1 -在同一异源表达系统中均未对该药物产生应答，提示probenecid是TRPV2的特异性激活剂。probenecd诱发的反应也在培养的三叉神经细胞的不同亚群中重现，这些神经元对2-氨基乙氧基二苯硼酸盐（一种TRPV - 1-3激活剂）有反应。probenid -sensitive neuron主要分布在中大直径的群体中，这与之前TRPV2免疫定位的观察结果一致。在体内实验中，在炎症条件下，probenecid会引起伤害性行为。这些结果表明，TRPV2被probenecid特异性激活，这种化学物质可能有助于研究与疼痛相关的TRPV2功能。2007爱思唯尔爱尔兰有限公司版权所有。
Temperature-activated transient receptor potential ion channels (thermoTRPs) are known to function as ambient temperature sensors and are also involved in peripheral pain sensation. The thermoTRPs are activated by a variety of chemicals, of which specific activators have been utilized to explore the physiology of particular channels and sensory nerve subtypes. The use of capsaicin for TRPV1 is an exemplary case for nociceptor studies. In contrast, specific agents for another vanilloid subtype channel, TRPV2 have been lacking. Here, we show that probenecid is able to activate TRPV2 using electrophysiological and calcium imaging techniques with TRPV2-expressing HEK293T cells. Five other sensory thermoTRPs-TRPV1, TRPV3, TRPV4, TRPM8 and TRPA1-failed to show a response to this drug in the same heterologous expression system, suggesting that probenecid is a specific activator for TRPV2. Probenecid-evoked responses were also reproduced in a distinct subset of cultured trigeminal neurons that were responsive to 2-aminoethoxydiphenyl borate, a TRPV 1-3 activator. The probenecid-sensitive neurons were mainly distributed in a medium to large-diameter population, in agreement with previous observations with TRPV2 immunolocalization. Under inflammation, probenecid elicited nociceptive behaviors in in vivo assays. These results suggest that TRPV2 is specifically activated by probenecid and that this chemical might be useful for investigation of pain-related TRPV2 function. (c) 2007 Elsevier Ireland Ltd. All rights reserved.