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Study of relationship between intracellular signal transduction system and bile secretion

细胞内信号转导系统与胆汁分泌关系的研究

基本信息

批准号：
07670606
负责人：
HIGASHI Katsuyoshi
金额：
$ 1.66万
依托单位：
Nagoya City University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
1995
资助国家：
日本
起止时间：
1995 至 1996
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-07670606/
关键词：
isolated hepatocytes vasopressin phospholipase C bile secretion HRP protein kinase A ursodeoxycholate protein kinase A ウイリデオキシコール酸

项目摘要

In isolated rat hepatocytes, addition of vasopressin causes the inositol trisphosphate formation and increase of intracellular Ca^<2+> concentration ([Ca^<2+>]c) in a dose dependent manner. In the experiments with perfused liver, infusion of vasopressin caused transient increase and prominent decrease in bile secretion, resulting in cholestasis. Flow of horseradish peroxidase (HRP) into the bile increased by the treatment with vasopressin in a dose dependent manner. These data indicate that increase of [Ca^<2+>]c induces cholestasis, but enhances vesicle transport in rat hepatocytes.Protein kinase A activation by the treatment with cAMP analog clearly enhanced vasopressin induced [Ca^<2+>]c increase in isolated hepatocytes. cAMP analog increased bile secretion in perfused liver. However, treatment with cAMP analog caused a marked enhancement in transient increase and the subsequent decrease of bile secretion. Addition of low concentration of vasopressin (10pM) does not affect [Ca^<2+>]c and bile secretion, but increase of [Ca^<2+>]c and decrease of bile secretion were observed by the treatment with cAMP analog, suggesting the close relationship between [Ca^<2+>]c increase and cholestasis. However, tauroursodeoxycholate (TUDCA) prevented the enhancement effect of cAMP analog on [Ca^<2+>]c increase and cholestasis. In addition, TUDCA inhibits the activation of protein kinase A by glucagon. These data indicate that TUDCA may act as a inhibitory agent of protein kinase A.

在离体大鼠肝细胞中，加压素的加入引起三磷酸肌醇的形成和细胞内Ca^2+浓度（[Ca^2+]c）的增加，并呈剂量依赖性。在灌注肝脏的实验中，加压素的输注引起胆汁分泌的短暂增加和显著减少，导致胆汁淤积。辣根过氧化物酶（HRP）流入胆汁中的增加与加压素的治疗剂量依赖性的方式。这些数据表明，[Ca^<2 +>]c的增加诱导胆汁淤积，但在大鼠肝细胞中增强囊泡转运。cAMP类似物增加灌注肝脏中的胆汁分泌。然而，用cAMP类似物处理引起胆汁分泌短暂增加和随后减少的显著增强。低浓度加压素（10 pM）对胆汁分泌和[Ca^<2+>]c无影响，而cAMP类似物可使[Ca^<2+>]c升高，胆汁分泌减少，提示[Ca^<2+>]c升高与胆汁淤积密切相关。然而，牛磺熊去氧胆酸盐（TUDCA）阻止了cAMP类似物对[Ca^<2+>]c升高和胆汁淤积的增强作用。此外，TUDCA抑制胰高血糖素对蛋白激酶A的激活。这些数据表明，TUDCA可能作为蛋白激酶A的抑制剂。