Increased acid-sensing ion channel ASIC-3 in inflamed human intestine
Increased acid-sensing ion channel ASIC-3 in inflamed human intestine
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DOI：
10.1097/00042737-200108000-00003
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发表时间：
2001-08
影响因子：
2.1
通讯作者：
Y. Yiangou;P. Facer;Jacqueline A. M. Smith;L. Sangameswaran;R. Eglen;R. Birch;C. Knowles;N. Williams;P. Anand
中科院分区：
文献类型：
--
作者：
Y. Yiangou;P. Facer;Jacqueline A. M. Smith;L. Sangameswaran;R. Eglen;R. Birch;C. Knowles;N. Williams;P. Anand
目的酸敏感离子通道(ASICs)由大鼠感觉神经元表达，可能介导炎症或损伤后组织酸中毒引起的疼痛。我们的目的是用免疫化学技术检测ASICs在人类肠道和背根神经节中的分子形态和定位，并测量炎症和损伤的影响。设计与方法应用特异性亲和力纯化的ASIC抗体，用免疫印迹和免疫组织化学方法，对炎性克罗恩病肠和损伤的人背根神经节进行研究。结果免疫印迹显示，在全层炎性肠段、分离的肌层和粘膜层，ASIC-3 55 kDa条带的平均相对光密度(ASIC-1或ASIC-2)显著增加3倍。炎症肠肌间神经丛和粘膜下神经丛的免疫反应密度和ASIC-3阳性神经元数量也有相应增加的趋势。在背根神经节，所有ASICs的免疫反应仅限于一小部分(约50%)小直径(伤害性感受器)感觉神经元，损伤后的免疫反应一般较弱。结论ASIC-3在炎性肠炎中的升高提示其在疼痛或运动障碍中起作用，对此ASIC可作为新的治疗靶点。
Objectives Acid-sensing ion channels (ASICs) are expressed by rat sensory neurons and may mediate pain associated with tissue acidosis after inflammation or injury. Our aim was to examine the molecular forms and localization of ASICs in human intestine and dorsal root ganglia using immunochemical techniques, and to measure the effects of inflammation and injury. Design and methods Inflamed Crohn's disease intestine and injured human dorsal root ganglia, with appropriate controls, were studied by Western blotting and immunohistochemistry, using specific affinity-purified ASIC antibodies. Results In the Western blot, there was a significant three-fold increase in the mean relative optical density of the ASIC-3 55-kDa band (but not ASIC-1 or ASIC-2) in full-thickness inflamed intestine, as well as in separated muscle and mucosal layers. There was a corresponding trend for an increased immunoreactive density and increased number of ASIC-3-positive neurons in the myenteric and sub-mucous plexus of inflamed intestine. In dorsal root ganglia, immunoreactivity for all ASICs was restricted to a sub-population (about 50%) of small-diameter (nociceptor) sensory neurons, and was generally less intense after injury. Conclusions Increased ASIC-3 in inflamed intestine suggests a role in pain or dysmotility, for which ASICs represent new therapeutic targets.