Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice
Brain-derived neurotrophic factor enhances the contraction of intestinal muscle strips induced by SP and CGRP in mice
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脑源性神经营养因子增强SP和CGRP诱导的小鼠肠肌条收缩
DOI：
10.1016/j.regpep.2012.07.001
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发表时间：
2012-10-10
影响因子：
--
通讯作者：
Li, Yan-qing
中科院分区：
文献类型：
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作者：
Chen, Fei-xue;Yu, Yan-bo;Li, Yan-qing
背景和目的：脑源性神经营养因子（BDNF）存在于多种动物的肠道中。它对内脏痛觉过敏的影响已在一定程度上进行了研究，但有限的研究集中在肠道运动。本研究旨在探讨BDNF对小鼠肠运动的影响。用离体多导生理记录仪记录肠平滑肌条的收缩，评价肠运动。首先，阐明了P物质（SP）、降钙素基因相关肽（CGRP）和乙酰胆碱（ACh）在LM条收缩中的作用。然后给予外源性BDNF，观察SP/CGRP/ACh对肌条收缩的影响。最后，我们引入杂合子BDNF+/-小鼠和TrkB抗体，研究内源性BDNF对SP/CGRP/ACh诱导的肠道运动的影响。SP（10（-8）-10（-6）mol L-1），CGRP（10（-8）-10（-7）mol L ~（-1））和ACh（10（-8）-10（-6）mol L ~（-1））剂量依赖性地引起回肠和远端结肠LM条的收缩，而CGRP的兴奋效应之前是短暂的抑制。10（-6）mol L ~（-1）CGRP抑制LM条的收缩。外源性BDNF（10（-8）mol L ~（-1））预处理显著增强SP（10（-9）-10（-7）mol L ~（-1））和CGRP（10（-8）-10（-9）mol L ~（-1））引起的LM条收缩。外源性BDNF对ACh（10（-9）~ 10（-7）mol L-1）引起的收缩无影响。Sr（10（-8）-10（-6）mol L ~（-1））和CGRP（10（-8）-10（-7）mol L ~（-1））对BDNF+/-小鼠回肠和远端结肠平滑肌条收缩的兴奋作用明显减弱，而ACh（10（-8）-10（-6）mol L-1）对BDNF+/-小鼠和BDNF+/+小鼠LM条的影响无差异。TrkB的单克隆抗体（TrkB-Ab）能显著减弱SP和CGRP对LM条收缩的兴奋作用，而不影响ACh的兴奋作用。结论和推论：这些数据阐明了SP、ACh的兴奋作用和CGRP对小鼠肠运动的双向作用，并证实了BDNF通过增强SP/CGRP的兴奋作用而加速肠运动的重要作用。(C)2012爱思唯尔有限公司版权所有。
Background and aims: Brain-derived neurotrophic factor (BDNF) has been found in the intestinal tract of a variety of species. Its effects on visceral hyperalgesia have been examined to some degree, but limited studies have focused on gut motility. The aim of the present study was to investigate the effects of BDNF on gut motility of mice.Methods: Longitudinal muscle (LM) strips were prepared from mice ileum and distal colon. The motility of gut was evaluated by the contraction of LM strips, which was recorded by a polyphisograph in vitro. Firstly, the roles of substance P (SP), calcitonin gene-related peptide (CGRP), and acetylcholine (ACh) on the contraction of LM strips were clarified. Then the exogenous BDNF was administered, and the alterations of SP/CGRP/ACh-induced contractions of the muscle strips were explored. Finally, heterozygous BDNF+/- mice and antibody of TrkB were introduced to investigate the role of endogenous BDNF on the SP/CGRP/ACh-induced gut motility.Key results: SP (10(-8)-10(-6) mol L-1), CGRP (10(-8)-10(-7) mol L-1) and ACh (10(-8)-10(-6) mol L-1) dose-dependently caused the contraction of LM strips from ileum and distal colon, while the excitatory effect of CGRP was preceded by a transient inhibition. But 10(-6) mol L-1 CGRP inhibited the contraction of LM strips. Pretreatment with exogenous BDNF (10(-8) mol L-1) remarkably enhanced the contraction of LM strips induced by SP (10(-9)-10(-7) mol L-1) and CGRP (10(-8)-10(-9) mol L-1). However, exogenous BDNF couldn't affect the contraction induced by ACh (10(-9)-10(-7) mol L-1). The excitatory effects of Sr (10(-8)-10(-6) mol L-1) and CGRP (10(-8)-10(-7) mol L-1) on the contractions of LM strips from ileum and distal colon were significantly attenuated in BDNF+/- mice compared with those in BDNF+/+ mice, while no difference of the effects of ACh (10(-8)-10(-6) mol L-1) on LM strips was observed between BDNF+/- mice and BDNF+/+ mice. The monoclonal antibody of TrkB (TrkB-Ab) dramatically attenuated the excitatory effects of SP and CGRP on the contractions of LM strips, without affecting the excitatory effects of ACh.Conclusions and inferences: These data clarified the excitatory effects of SP. ACh and bilateral effects of CGRP on gut motility of mice and confirmed an essential role of BDNF on accelerating gut motility by enhancing the excitatory effects of SP/CGRP. (C) 2012 Elsevier B.V. All rights reserved.