Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia
Contribution of transient receptor potential vanilloid subfamily 1 to endothelin-1-induced thermal hyperalgesia
复制标题
DOI：
10.1016/j.neuroscience.2008.04.010
复制
发表时间：
2008-06-26
期刊：
影响因子：
3.3
通讯作者：
Namiki, A.
中科院分区：
文献类型：
--
作者：
Kawamata, T.;Ji, W.;Namiki, A.
内皮素-1（ET-1）在外周痛觉过程中起重要作用。然而，ET-1的伤害性作用的机制尚未完全阐明。在这项研究中，我们研究了瞬时受体电位香草酸亚家族1（TRPV 1）的ET-1诱导的热痛觉过敏的贡献。足底ET-1诱导的热痛觉过敏通过评估对伤害性热刺激的缩爪潜伏期来检查。在电生理研究中，采用全细胞膜片钳技术，以表达内皮素A型受体（ET（A））和TRPV 1的人胚肾293（HEK 293）细胞为研究对象，研究了ET-1和TRPV 1的相互作用。足底ET-1（3，10和30 pmol）产生热痛觉过敏的剂量依赖性方式。抑制ETA和蛋白激酶C（PKC）可减轻热痛敏，而抑制ET（B）则无此作用。与野生型小鼠相比，TRPV 1缺陷型小鼠中ET-1诱导的热痛觉过敏显著减弱。在电压钳实验中，10 nM辣椒素在表达TRPV 1和ETA的HEK 293细胞中诱发小的内向电流。在ET-1存在下，辣椒素产生更大的电流响应（P
Endothelin-1 (ET-1) plays an important role in peripheral pain processing. However, the mechanisms of the nociceptive action of ET-1 have not been fully elucidated. In this study, we investigated the contribution of transient receptor potential vanilloid subfamily 1 (TRPV1) to ET-1-induced thermal hyperalgesia. Intraplantar ET-1-induced thermal hyperalgesia was examined by assessing the paw withdrawal latency to noxious heat stimuli. In electrophysiological study, whole-cell patch-clamp recordings were performed to investigate the interaction of ET-1 and TRPV1 using human embryonic kidney 293 (HEK293) cells expressing endothelin type A receptor (ET(A)) and TRPV1. Intraplantar ET-1 (3, 10 and 30 pmol) produced thermal hyperalgesia in a dose-dependent manner. Thermal hyperalgesia was attenuated by the inhibition of ETA and protein kinase C (PKC) but not that of ET(B). ET-1-induced thermal hyperalgesia was significantly attenuated in TRPV1-deficient mice compared with that in wild-type mice. In voltage-clamp experiments, 10 nM capsaicin evoked small inward currents in HEK293 cells expressing TRPV1 and ETA. In the presence of ET-1, capsaicin produced much larger current responses (P