Nitric oxide blocks bile canalicular contraction by inhibiting inositol trisphosphate-dependent calcium mobilization.
Nitric oxide blocks bile canalicular contraction by inhibiting inositol trisphosphate-dependent calcium mobilization.
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一氧化氮通过抑制肌醇三磷酸依赖性钙动员来阻止胆小管收缩。
DOI：
10.1016/0016-5085(95)90459-x
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发表时间：
1995
期刊：
影响因子：
29.4
通讯作者：
Arias,IM
中科院分区：
文献类型：
--
作者：
Dufour,JF;Turner,TJ;Arias,IM
背景/目的：胆管收缩的生化机制与平滑肌收缩的生化机制相似。收缩遵循肌醇-1，4，5-三磷酸（InsP 3）依赖性Ca 2+释放，其激活肌动蛋白-肌球蛋白相互作用。一氧化氮是通过5′-环磷酸鸟苷（cGMP）作用的肌肉松弛剂，并且在暴露于内毒素和细胞因子的肝细胞中产生。本研究的目的是探讨一氧化氮对小管收缩的影响，并确定cGMP干扰收缩signal.MethodsThe小管运动在大鼠肝细胞双的机制，通过显微图像分析，和细胞内Ca 2+荧光显微镜测定。采用放射免疫法和高压液相色谱法测定cGMP和InsP 3。通过过滤和灌流assays. ResultsThe释放一氧化氮的化合物刺激肝细胞cGMP的产生，并通过抑制细胞内Ca 2+的增加，防止激动剂诱导的收缩，测定从肝匀浆中的Ca 2+释放。cGMP类似物溴-cGMP阻止收缩和Ca 2+的增加。溴-cGMP略微降低InsP 3的产生。cGMP阻断InsP 3依赖的Ca 2+释放从internal stores.ConclusionsThese研究结果表明，一氧化氮干扰Ca 2+信号cGMP介导的抑制InsP 3受体/Ca 2+通道和肝细胞生产的一氧化氮可能是胆汁淤积通过损害小管运动。
Background/AimsThe biochemical mechanism of bile canalicular contraction is similar to that of smooth muscle contraction. Contraction follows inositol-1,4,5-trisphosphate (InsP3)-dependent Ca2+release, which activates actin-myosin interactions. Nitric oxide is a myorelaxant through the actions of 5′-cyclic guanosine monophosphate (cGMP) and is produced in hepatocytes exposed to endotoxin and cytokines. The aim of this study was to investigate the effect of nitric oxide on canalicular contraction and to determine the mechanism by which cGMP interferes with the contractile signal.MethodsThe canalicular motility in rat hepatocyte doublets was measured by microscopic image analysis, and intracellular Ca2+was measured by fluorescence microscopy. cGMP and InsP3were determined by radio-immunoassay and high-pressure liquid chromatography. Ca2+release from liver homogenate was measured by filtration and superfusion assays.ResultsCompounds that release nitric oxide stimulated hepatocellular production of cGMP and prevented agonist-induced contraction by inhibiting the increase in intracellular Ca2+. The cGMP analogue bromo-cGMP prevented contraction and the increase in Ca2+. Bromo-cGMP marginally decreased InsP3production. cGMP blocked InsP3-dependent Ca2+release from internal stores.ConclusionsThese findings suggest that nitric oxide interferes with Ca2+signals by cGMP-mediated inhibition of the InsP3receptor/Ca2+channel and that hepatocellular production of nitric oxide may be cholestatic by impairing canalicular motility.
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大鼠肝细胞双联体中的细胞外 ATP、细胞内钙和小管收缩
影响因子：
13.5
作者：
T. Kitamura;U. Brauneis;Z. Gatmaitan;I. Arias
通讯作者：
I. Arias
微丝功能障碍可能是肝内胆汁淤积的原因。
影响因子：
29.4
作者：
M. J. Phillips;M. Oda;E. Mak;M. M. Fisher;K. Jeejeebhoy
通讯作者：
K. Jeejeebhoy
Yoshida,Y.：“环状 GMP 依赖性蛋白激酶通过 240 kDa 蛋白的磷酸化刺激血管平滑肌的质膜 Ca2 泵 ATP 酶。”
DOI：
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发表时间：
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期刊：
影响因子：
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作者：
通讯作者：
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人肝细胞中诱导型一氧化氮合酶的分子克隆和表达
DOI：
10.1073/pnas.90.8.3491
发表时间：
1993-04-15
影响因子：
11.1
作者：
GELLER, DA;LOWENSTEIN, CJ;BILLIAR, TR
通讯作者：
BILLIAR, TR
环 GMP 对凝血酶刺激的人血小板分泌、多磷酸肌醇水解和钙动员的抑制作用。
DOI：
--
发表时间：
1986
期刊：
Biochemical and Biophysical Research Communications - BBRC
影响因子：
--
作者：
Shigeru Nakashima;T. Tohmatsu;H. Hattori;Yukio Okano;Y. Nozawa
通讯作者：
Y. Nozawa