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Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats
Yan, Chi; Xin-Guang, Liu; Hua-Hong, Wang; Jun-Xia, Li; Yi-Xuan, Li
关键词5-hydroxytryptamine Receptor 4 Serotonin Serotonin Transport Protein Visceral Hypersensitivity
刊名BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH
2012-10-01
DOI10.1590/S0100-879X2012007500122
45期:10页:948-954
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biology ; Medicine, Research & Experimental
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
研究领域[WOS]Life Sciences & Biomedicine - Other Topics ; Research & Experimental Medicine
关键词[WOS]IRRITABLE-BOWEL-SYNDROME ; SMALL-INTESTINE ; GASTROINTESTINAL MOTILITY ; COLON IRRITATION ; EXPRESSION ; 5-HYDROXYTRYPTAMINE ; COLITIS ; ARTICLE ; AVAILABILITY ; MODULATION
英文摘要

Visceral hypersensitivity plays an important role in motor and sensory abnormalities associated with irritable bowel syndrome, but the underlying mechanisms are not fully understood. The present study was designed to evaluate the expression of the 5-HT4 receptor and the serotonin transporter (SERT) as well as their roles in chronic visceral hypersensitivity using a rat model. Neonatal male Sprague-Dawley rats received intracolonic injections of 0.5% acetic acid (0.3-0.5 mL at different times) between postnatal days 8 and 21 to establish an animal model of visceral hypersensitivity. On day 43, the threshold intensity for a visually identifiable contraction of the abdominal wall and body arching were recorded during rectal distention. Histological evaluation and the myeloperoxidase activity assay were performed to determine the severity of inflammation. The 5-HT4 receptor and SERT expression of the ascending colon were monitored using immunohistochemistry and Western blot analyses; the plasma 5-HT levels were measured using an ELISA method. As expected, transient colonic irritation at the neonatal stage led to visceral hypersensitivity, but no mucosal inflammation was later detected during adulthood. Using this model, we found reduced SERT expression (0.298 +/- 0.038 vs 0.634 +/- 0.200, P < 0.05) and increased 5-HT4 receptor expression (0.308 +/- 0.017 vs 0.298 +/- 0.021, P < 0.05). Treatment with fluoxetine (10 mg.kg(-1).day(-1), days 36-42), tegaserod (1 mg.kg(-1).day(-1), day 43), or the combination of both, reduced visceral hypersensitivity and plasma 5-HT levels. Fluoxetine treatment increased 5-HT4 receptor expression (0.322 +/- 0.020 vs 0.308 +/- 0.017, P < 0.01) but not SERT expression (0.219 +/- 0.039 vs 0.298 +/- 0.038, P = 0.654). These results indicate that both the 5-HT4 receptor and SERT play a role in the pathogenesis of visceral hypersensitivity, and its mechanism may be involved in the local 5-HT level.

语种英语
所属项目编号30600275
资助者National Natural Science Foundation of China ; National Natural Science Foundation of China
WOS记录号WOS:000308408600010
引用统计
被引频次:10[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/56281
专题北京大学第一临床医学院_消化科
作者单位Peking Univ, Dept Gastroenterol, Hosp 1, Beijing 100034, Peoples R China
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Yan, Chi,Xin-Guang, Liu,Hua-Hong, Wang,et al. Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats[J]. BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH,2012,45(10):948-954.
APA Yan, Chi,Xin-Guang, Liu,Hua-Hong, Wang,Jun-Xia, Li,&Yi-Xuan, Li.(2012).Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats.BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH,45(10),948-954.
MLA Yan, Chi,et al."Effect of the 5-HT4 receptor and serotonin transporter on visceral hypersensitivity in rats".BRAZILIAN JOURNAL OF MEDICAL AND BIOLOGICAL RESEARCH 45.10(2012):948-954.
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