Elucidation of molecular mechanisms of pathophysiological pain via nociceptive channels and establishment of pain-evaluating system

我们从两栖动物和鸡中克隆了编码伤害感受通道的cDNA并构建了表达载体。为了阐明这些受体的病理生理意义，我们建立了伤害感觉评价系统。利用该系统，我们发现了TRPV1的辛辣化合物辣椒素的识别位点。热带棘猴TRPA1的功能表达和特征分析表明，两栖动物TRPA1与同质同源物相比具有热敏性。通过对人和小鼠TRPA1的分析发现，环境刺激物镉和内源性炎性气体信使硫化氢可激活TRPA1通道，引起急性疼痛。我们通过诱变研究确定了与这些化学敏感性有关的氨基酸残基。这些数据表明，痛觉性TRP通道是炎症性病理生理性疼痛的重要分子。

We cloned cDNA encoding nociceptive channels from amphibian and chicken and constructed expression vectors. We established nociception-evaluating system for elucidation of the pathophysiological significance of these receptors. Using this system, we found that the recognition sites for capsaicin, a pungent compound for TRPV1. Functional expression and characterizing of X. troplicalis TRPA1 revealed that amphibian TRPA1 showed heat sensitivity in contrast to homoeothermic homologues. By analyzing human and mouse TRPA1s, Cadmium, an environmental irritant and hydrogen sulfide, en endogenous inflammatory gasomessenger, could activate TRPA1 channel resulting in elicitation of acute pain. We identified amino acid residues regarding these chemical sensitivities by mutagenetic studies. These data suggest that nociceptive TRP channels are important molecule especially for inflammation-induced pathophysiological pain.