α7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis
α7-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis
复制标题
DOI：
10.1152/ajpgi.00175.2010
复制
发表时间：
2010-09-01
影响因子：
4.5
通讯作者：
Akbarali, Hamid I.
中科院分区：
文献类型：
--
作者：
Abdrakhmanova, Galya R.;AlSharari, Shakir;Akbarali, Hamid I.
Abdrakhmanova GR, AlSharari S, Kang M, Damaj MI, Akbarali HI。α (7)- nachr介导的实验性结肠炎结肠背根神经节神经元高兴奋性的抑制。[J] .中国生物医学工程学报，2010,31(2):481 - 481。首次发表于2010年7月1日；doi: 10.1152 / ajpgi.00175.2010。-尼古丁透皮贴片治疗溃疡性结肠炎的对照临床试验已显示可改善结肠炎的组织学和整体临床评分。本研究报告了尼古丁（1 μ M）在体外抑制右旋糖酐硫酸钠（DSS）诱导的小鼠急性结肠炎症模型中结肠背根神经节（DRG） （L-1-L-2）神经元的高兴奋性。尼古丁逐渐降低结肠炎小鼠再生多尖峰动作电位为单动作电位。在α(7)-尼古丁乙酰胆碱受体（nAChR）拮抗剂甲基licaconitine存在时，尼古丁对炎症神经元高兴奋性的作用被阻断，而α (7)-nAChR激动剂胆碱诱导的作用与尼古丁相似。与这些发现一致，尼古丁未能抑制dss处理的α(7)敲除小鼠结肠DRG神经元的高兴奋性。此外，与dss处理的C57BL/J6小鼠相比，dss处理的α(7)敲除小鼠的结肠DRG神经元具有更低的流变酶（分别为10 +/- 5和77 +/- 13 pA）和电流阈值（分别为28 +/- 4和103 +/- 8 pA）水平。本研究的一个有趣的观察结果是，来自α(7)敲除小鼠的12个结肠DRG （L1-L2）神经元中有8个表现出多峰动作电位放电，而野生型神经元则没有。总之，我们的研究结果表明，在小鼠急性结肠炎症模型中，低浓度1 μ M的尼古丁通过激活α (7)- nachr来抑制炎症结肠DRG神经元的体外高兴奋性。
Abdrakhmanova GR, AlSharari S, Kang M, Damaj MI, Akbarali HI. alpha(7)-nAChR-mediated suppression of hyperexcitability of colonic dorsal root ganglia neurons in experimental colitis. Am J Physiol Gastrointest Liver Physiol 299: G761-G768, 2010. First published July 1, 2010; doi: 10.1152/ajpgi.00175.2010.-Controlled clinical trials of nicotine transdermal patch for treatment of ulcerative colitis have been shown to improve histological and global clinical scores of colitis. Here we report that nicotine (1 mu M) suppresses in vitro hyperexcitability of colonic dorsal root ganglia (DRG) (L-1-L-2) neurons in the dextran sodium sulfate (DSS)-induced mouse model of acute colonic inflammation. Nicotine gradually reduced regenerative multiple-spike action potentials in colitis mice to a single action potential. Nicotine's effect on hyperexcitability of inflamed neurons was blocked in the presence of an alpha(7)-nicotinic acetylcholine receptor (nAChR) antagonist, methyllicaconitine, while choline, the alpha(7)-nAChR agonist, induced a similar effect to that of nicotine. Consistent with these findings, nicotine failed to suppress hyperexcitability in colonic DRG neurons from DSS-treated alpha(7) knockout mice. Furthermore, colonic DRG neurons from DSS-treated alpha(7) knockout mice were characterized by lower rheobase (10 +/- 5 vs. 77 +/- 13 pA, respectively) and current threshold (28 +/- 4 vs. 103 +/- 8 pA, respectively) levels than DSS-treated C57BL/J6 mice. An interesting observation of this study is that 8 of 12 colonic DRG (L1-L2) neurons from control alpha(7) knockout mice exhibited multiple-spike action potential firing while no wild-type neurons did. Overall, our findings suggest that nicotine at low 1 mu M concentration suppresses in vitro hyperexcitability of inflamed colonic DRG neurons in a mouse model of acute colonic inflammation via activation of alpha(7)-nAChRs.