Inhibitory modulation of the pain sensor protein, TRPA1

瞬时受体电位（TRP）通道亚型V1 （TRPV1）和A1 （TRPA1）已知在感觉神经元上表达，并对温度、pH值和某些有毒化学物质的局部应用变化作出反应。在本研究中，我们研究了这些TRP通道的抑制调节机制。以下是本研究的主要发现。我们发现青蒿素或白藜芦醇可以抑制TRPA1。其机制可能是由于细胞膜上TRPA1通道密度的降低。2. Pinosylvin甲基醚可以通过改变EC50抑制TRPV1，但不能通过改变辣椒素诱导电流的最大响应来抑制TRPV1。3. 依托度酸可以通过半胱氨酸残基的共价修饰直接激活并随后使TRPA1脱敏。这些数据表明，TRP通道调节的抑制机制是多种多样和复杂的。

The transient receptor potential (TRP) channel subtype V1 (TRPV1) and A1 (TRPA1) are known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals. In this study, we investigated mechanisms of inhibitory modulation of these TRP channels. Following is the major findings of this study.1. We found that artemin or resveratrol can inhibit TRPA1. The mechanism is likely due to a decreasing of the channel density of TRPA1 on cell membranes. 2. Pinosylvin methyl ether can inhibit TRPV1 by changing the EC50, but not the maximum response of capsaicin-induced currents. 3. Etodolac can direct activate and subsequently desensitize TRPA1 through a covalent modification of cysteine residues. These data indicate that the inhibitory mechanism of modulation of TRP channels are various and complicated.