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Food allergy and immunologic disease in the intestine : the role of primary afferent neurons in the intestine

食物过敏和肠道免疫疾病：肠道初级传入神经元的作用

基本信息

批准号：
14570065
负责人：
KADOWAKI Makoto
金额：
$ 1.86万
依托单位：
TOYAMA MEDICAL AND PHARMACEUTICAL UNIVERSITY (2004)Nara Medical University (2002-2003)
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2004
项目状态：
已结题

项目摘要

The aim of this study was to determine the action of capsaicin in isolated rat intestine and the origin of nerve fibers expressing transient receptor potential vanilloid 1 (TRPV1 : capsaicin receptor) in the rat jejunum by combination of functional and immunohistochemical experiments. Capsaicin (1μM) produced a prolonged relaxation response (52.8±15.3% of the relaxation response to papaverine, mean ± S.D., n=27) of the isolated jejunum in the presence of atropine and guanethidine. Pretreatment with the TRPV1 antagonist, capsazepine (10μM) and ruthenium red (3μM) significantly reduced the relaxation response to capsaicin by 78% (P<0.01) and 38% (P<0.05), respectively. Tetrodotoxin and calcitonin gene-related peptide (CGRP)-desensitization significantly reduced the response to capsaicin by 72% (P<0.01) and 42% (P<0.01), respectively. Therefore, we investigated the distribution of TRPV1-immunoreactivity (IR) in the myenteric plexus of the rat jejunum. Using antisera raised against either the N-terminal or C-terminal domains of rat TRPV1, TRPV1-IR was present in the nerve fibers, but not in the cell bodies of myenteric neurons. These TRPV1-immunoreactive nerve fibers were running in myenteric ganglia and their interconnecting strands. Most TRPV1-immunoreactive nerve fibers showed CGRP-IR, whereas few VR1-immunoreactive nerve fibers showed substance P-IR. After chronic denervation of the extrinsic nerve supply to the jejunum, both the relaxation response to capsaicin and TRPV1-immunoreactive nerve fibers completely disappeared. These findings indicate that these TRPV1-immunoreactive nerve fibers in the rat jejunum derive from extrinsic neurons and that activation of TRPV1 produces the relaxation response in the rat jejunum, at least in part, through the release of CGRP from nerve fibers expressing TRPV1.

本研究的目的是确定辣椒素在离体大鼠肠和神经纤维的起源表达瞬时受体电位香草素1（TRPV 1：辣椒素受体）在大鼠空肠的功能和免疫组化实验相结合的行动。辣椒素（1μM）产生延长的舒张反应（罂粟碱舒张反应的52.8±15.3%，平均值± S.D.，n=27）的离体空肠中的阿托品和乙啶的存在下。用TRPV 1拮抗剂辣椒平（10μM）和钌红（3μM）预处理可使辣椒素引起的舒张反应分别降低78%（P<0.01）和38%（P<0.05）。河豚毒素和降钙素基因相关肽（CGRP）脱敏显著降低了对辣椒素的反应，分别为72%（P<0.01）和42%（P<0.01）。因此，我们研究了TRPV 1免疫反应（IR）在大鼠空肠肌间神经丛的分布。使用抗血清对大鼠TRPV 1的N-末端或C-末端结构域，TRPV 1-IR存在于神经纤维，但不是在肌间神经元的细胞体。这些TRPV 1免疫反应阳性神经纤维在肌间神经节及其相互连接的股。大多数TRPV 1免疫反应神经纤维显示CGRP-IR，而少数VR 1免疫反应神经纤维显示P物质IR。慢性去神经支配空肠后，辣椒素和TRPV 1免疫反应神经纤维的松弛反应完全消失。这些研究结果表明，这些TRPV 1免疫反应神经纤维在大鼠空肠来自外源性神经元和TRPV 1的激活产生的松弛反应，在大鼠空肠，至少部分，通过释放CGRP从神经纤维表达TRPV 1。

项目成果

期刊论文数量（5）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Localization of neurokinin 1 receptor (NK1R) immunoreactivity in rat esophagus

大鼠食管中神经激肽 1 受体 (NK1R) 免疫反应性的定位

DOI：
发表时间：
2004
期刊：
The Journal of Comparative Neurology 478(1)
影响因子：
0
作者：
Hirofumi Kuramoto;Yukio Oomori Hiroshi Murabayashi;Makoto Kadowaki;Shin-Ichiro Karaki;Atsukazu Kuwahara
通讯作者：
Atsukazu Kuwahara

Combined determination with functionnal and morphological studies of origin of nerve fibers expressing transient receptor potential vanilloid 1 in the myenteric plexus of the rat jejunum.

结合功能和形态学研究确定大鼠空肠肌间神经丛中表达瞬时受体电位香草酸 1 的神经纤维的起源。