Involvement of inflammatory cells on the dysmotility of gastrointestinal smooth muscles in experimental colitis model animals.
炎症细胞参与实验性结肠炎模型动物胃肠平滑肌运动障碍。
基本信息
- 批准号:15580260
- 负责人:
- 金额:$ 2.43万
- 依托单位:
- 依托单位国家:日本
- 项目类别:Grant-in-Aid for Scientific Research (C)
- 财政年份:2003
- 资助国家:日本
- 起止时间:2003 至 2004
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
The mechanism of gastro-intestinal dysmotility in the inflammatory bowel disease has not been cleared. In this study, we examined the mechanism involved in the inflamed distal colon isolated from dextran sodium sulphate-induced ulcerative colitis model mouse (DSS-treated mouse). Although substance P-induced contraction was not changed, carbachol-induced contraction was reduced in DSS-treated mouse colon. Pre-incubation with NO synthase inhibitor, L-NMMA, cyclooxygenase inhibitor, indomethacin, or ATP-sensitive K^+ channel inhibitor, glibenclamide, did not recovered the carbachol-induced contraction in DSS-treated moue colon. In semi-quantitative RT-PCR experiments and Western blotting analysis, muscarinic M_3 receptor expressions were not changed. The Ca^<2+>-sensitization of contractile elements induced by carbachol with GTP or GTP_YS was reduced in the β-escin permeabilized DSS-treated mouse colon. Although the expression of proteins, such as rhoA, ROCK1 or ROCK2, that are involved i … More n G-protein coupled signaling in smooth muscles, were not changed, the expression of CPI-17, the functional proteins involved in the smooth muscle Ca^<2+>-sensitization, was significantly decreased in DSS-treated mouse colon. These results suggest that the suppression of carbachol-induced contraction in colitis mouse is attributable at lease partially to the increased activity of myosin phosphatase following the down regulation of CPI-17.Protease activated receptor-2 (PAR-2) is highly expressed in gastrointestinal tract and is activated by proteases released form mast cell and trypsin in intestinal lumen. PAR-2-acitivation induces a relaxation of colonic smooth muscle which is important for the motility. In order to elucidate the relationship of dysmotility of colon in ulcerative colitis model rat and PAR-2, we used the dextran sodium sulphate-induced ulcerative colitis model rat (DSS rat). In the control rat colon, trypsin induced relaxation of carbachol (CCh) and high KCl-induced contraction, which is completely resolved by the pretreatment of apamin. In DSS rat colon, these inhibitory effects of trypsin on CCh and high KCl-induced contraction were significantly reduced. In DSS rat colon, the relaxation induced by SLIGRL-NH was also reduced, but the inhibitory effect of EBIO-1, SK_<Ca> activator, has not been changed. In RT-PCR experiments, the expression of PAR-2 mRNA of colonic smooth muscle decreased in DSS rat from control rat. These results suggest that suppression of PAR-2 activator-induced relaxation in colitis rat colon is attributable to the down regulation of PAR-2 mRNA expression level. It is shown that gastro-intestinal-dysmotility is at least partially due to the down regulation of PAR-2 in IBD. Less
炎症性肠病中胃肠动力障碍的发生机制尚不清楚。在这项研究中,我们研究了从葡聚糖硫酸钠诱导的溃疡性结肠炎模型小鼠(DSS治疗小鼠)中分离的远端结肠炎症的机制。虽然P物质诱导的收缩没有改变,卡巴胆碱诱导的收缩减少DSS治疗的小鼠结肠。用NO合成酶抑制剂L-NMMA、环氧合酶抑制剂吲哚美辛或ATP敏感性K^+通道抑制剂格列本脲预孵育,不能恢复DSS处理的小鼠结肠中卡巴胆碱诱导的收缩。半定量RT-PCR和Western blotting分析表明,M_3受体的表达无明显变化。在β-七叶皂苷透化的DSS处理的小鼠结肠中,卡巴胆碱与GTP或GTP_YS诱导的收缩元件的Ca^<2+>敏感性降低。虽然相关蛋白质如rhoA、ROCK 1或ROCK 2的表达, ...更多信息 在DSS处理的小鼠结肠中,平滑肌中的G蛋白偶联信号没有改变,而参与平滑肌Ca^2+敏化的功能蛋白CPI-17的表达显著降低。这些结果表明,结肠炎小鼠对卡巴胆碱引起的收缩的抑制至少部分归因于CPI-17下调后肌球蛋白磷酸酶活性的增加。蛋白酶激活受体-2(PAR-2)在胃肠道中高度表达,并被肠腔中肥大细胞释放的蛋白酶和胰蛋白酶激活。PAR-2激活诱导结肠平滑肌松弛,这对于运动是重要的。为了探讨溃疡性结肠炎模型大鼠结肠动力障碍与PAR-2的关系,我们采用葡聚糖硫酸钠诱导的溃疡性结肠炎模型大鼠(DSS大鼠)。在对照大鼠结肠,胰蛋白酶引起的氨甲酰胆碱(CCh)和高氯化钾引起的收缩,这是完全解决的预处理的蜂毒肽。在DSS大鼠结肠中,胰蛋白酶对CCh和高KCl引起的收缩的这些抑制作用显著降低。在DSS大鼠结肠,SLIGRL-NH引起的舒张作用也减弱,但SK_1激活剂EBIO-1的抑制作用<Ca>没有改变。RT-PCR结果显示,DSS大鼠结肠平滑肌PAR-2 mRNA的表达较对照组明显降低。这些结果表明,抑制PAR-2激活剂诱导的结肠炎大鼠结肠舒张是由于PAR-2 mRNA表达水平下调。表明IBD时胃肠道动力障碍至少部分是由于PAR-2下调所致。少
项目成果
期刊论文数量(2)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Ohama T: "Chronic treatment with interleukin-1beta attenuates contractions by decreasing the activities of CPI-17 and MYPT-1 in intestinal smooth muscle"Journal of Biological Chemistory. 278(49). 48794-48804 (2003)
Ohama T:“长期使用白介素-1β 治疗可通过降低肠道平滑肌中 CPI-17 和 MYPT-1 的活性来减弱收缩”《生物化学杂志》。
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{{ truncateString('SATO Koichi', 18)}}的其他基金
Role of proton-sensing G protein-coupled receptors on microglial activation and neuronal cell survival in a mouse ischemia reperfusion model.
质子感应 G 蛋白偶联受体对小鼠缺血再灌注模型中小胶质细胞激活和神经元细胞存活的作用。
- 批准号:
15K06767 - 财政年份:2015
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Biochemical analysis of a DNA crosslink repair protein, FAN1
DNA 交联修复蛋白 FAN1 的生化分析
- 批准号:
26830128 - 财政年份:2014
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Young Scientists (B)
Role of proton-sensing G protein-coupled receptors on microglial activation and neuronal cell survival in a ischemic situation.
质子感应 G 蛋白偶联受体对缺血情况下小胶质细胞激活和神经元细胞存活的作用。
- 批准号:
24500435 - 财政年份:2012
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
The expression mechanism of protease activated receptors with inflammatory stimulations in intestinal myofibroblasts.
肠道肌成纤维细胞炎症刺激下蛋白酶激活受体的表达机制。
- 批准号:
22580334 - 财政年份:2010
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Involvement of ABCA1 transporter in the regulation of anti-atherogenic sphingosine-1-phosphate content in plasma and high-density lipoprotein
ABCA1转运蛋白参与血浆和高密度脂蛋白中抗动脉粥样硬化1-磷酸鞘氨醇含量的调节
- 批准号:
21591158 - 财政年份:2009
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Combination of a membrane reactor and microwave radiation for high efficient chemical reaction
膜反应器和微波辐射的结合实现高效化学反应
- 批准号:
21350085 - 财政年份:2009
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (B)
A study of autobiographical memory system : effects of aging on the stability of remembering.
自传体记忆系统的研究:衰老对记忆稳定性的影响。
- 批准号:
20530586 - 财政年份:2008
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Downregulatory mechanism of protease activated receptor in inflammatory bowel disease
炎症性肠病中蛋白酶激活受体的下调机制
- 批准号:
19580340 - 财政年份:2007
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Coupling of sphingosine 1-phosphate release with lipoprotein formation in central nervous system(CNS)
1-磷酸鞘氨醇释放与中枢神经系统 (CNS) 中脂蛋白形成的耦合
- 批准号:
18500287 - 财政年份:2006
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
Sphingosine 1-phosphate mediates some actions of lipoproteins that regulate neural functions.
1-磷酸鞘氨醇介导脂蛋白的一些调节神经功能的作用。
- 批准号:
14580736 - 财政年份:2002
- 资助金额:
$ 2.43万 - 项目类别:
Grant-in-Aid for Scientific Research (C)
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