Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin.
Inhibition of TRPA1 channel activity in sensory neurons by the glial cell line-derived neurotrophic factor family member, artemin.
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DOI：
10.1186/1744-8069-7-41
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发表时间：
2011-05-27
期刊：
影响因子：
3.3
通讯作者：
Dai Y
中科院分区：
文献类型：
--
作者：
Yoshida N;Kobayashi K;Yu L;Wang S;Na R;Yamamoto S;Noguchi K;Dai Y
瞬时受体电位（TRP）通道亚型A1（TRPA 1）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如异硫氰酸烯丙酯（AITC）的局部应用的变化作出反应。Artemin是一种神经元存活和分化因子，属于胶质细胞源性神经营养因子（GDNF）家族。据报道，TRPA 1和artemin都参与病理性疼痛的启动和维持。本研究采用全细胞膜片钳技术、原位杂交和行为学分析，研究了TRPA 1与artemin之间的功能相互作用。我们发现，85.8 ± 1.9%的TRPA 1表达神经元也表达GDNF家族受体α 3（GFR α3），87.5 ± 4.1%的GFRα3表达神经元为TRPA 1阳性。在全细胞膜片钳分析中，100 ng/ml artemin的短期处理显著抑制AITC诱导的TRPA 1电流。由artemin的作用产生的AITC的浓度-反应曲线表明，这种抑制不改变EC 50，但确实降低了AITC诱导的最大反应。此外，artemin预处理显著抑制足底注射AITC诱导的举爪次数，以及福尔马林诱导的疼痛行为。短期应用artemin可抑制TRPA 1通道的活性，并抑制其引起的连续性疼痛行为，提示artemin可能参与了感觉神经元的调节。
The transient receptor potential (TRP) channel subtype A1 (TRPA1) is known to be expressed on sensory neurons and respond to changes in temperature, pH and local application of certain noxious chemicals such as allyl isothiocyanate (AITC). Artemin is a neuronal survival and differentiation factor and belongs to the glial cell line-derived neurotrophic factor (GDNF) family. Both TRPA1 and artemin have been reported to be involved in pathological pain initiation and maintenance. In the present study, using whole-cell patch clamp recording technique, in situ hybridization and behavioral analyses, we examined the functional interaction between TRPA1 and artemin. We found that 85.8 ± 1.9% of TRPA1-expressing neurons also expressed GDNF family receptor alpha 3 (GFR α3), and 87.5 ± 4.1% of GFRα3-expressing neurons were TRPA1-positive. In whole-cell patch clamp analysis, a short-term treatment of 100 ng/ml artemin significantly suppressed the AITC-induced TRPA1 currents. A concentration-response curve of AITC resulting from the effect of artemin showed that this inhibition did not change EC50 but did lower the AITC-induced maximum response. In addition, pre-treatment of artemin significantly suppressed the number of paw lifts induced by intraplantar injection of AITC, as well as the formalin-induced pain behaviors. These findings that a short-term application of artemin inhibits the TRPA1 channel's activity and the sequential pain behaviors suggest a role of artemin in regulation of sensory neurons.
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影响因子：
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