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Physiological characteristics and molecular identity of HCO_3-conductance in pancreatic duct cells.

胰管细胞HCO_3-电导的生理特征和分子特性。

基本信息

批准号：
16590164
负责人：
ISHIGURO HIROSHI
金额：
$ 2.3万
依托单位：
Nagoya University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2004
资助国家：
日本
起止时间：
2004 至 2006
项目状态：
已结题

来源：
https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-16590164/
关键词：
pancreatic duct cell HCO_3^-transport HCO_3^-conductance Cl-HCO_3^- exchange CFTR SLC26A6 sweat CI concentration transgenic mice Cl^--HCO_3^- exchange Na^+-H^+ exchange cystic fibrosis 単離小葉間膵管短鎖アルコール cut-off effect 管腔膜モルモット

项目摘要

We have investigated molecular mechanisms for HCO_3-transport across the apical membrane of pancreatic duct cells using interlobular pancreatic duct segments isolated from guinea-pig and transgenic mice. As a clinical research, we examined polymorphisms of CFTR (cystic fibrosis transmembrane conductance regulator) in Japanese and established a simple method to measure concentration in sweat.1. Isolated pancreatic ducts from AF mice, a cystic fibrosis model that human AF508 mutation was introduced, had very poor capacity for cAMP-stimulated fluid secretion and stronger activity of of Na^+-H^+ exchange (NHE) in the apical membrane. The enhanced of apical NHE activity may be involved in decrease of pH and acidification of pancreatic juice.2. The HCO_3--influx mode of apical [CI^-]_i/[HCO_3^-]_o exchange was dramatically increased in slc26a6 null mice, whereas the HCO_3^--efflux mode of apical [C1^-]_i/[HCO_3^-]_o exchange was decreased in slc26a6 null mice, suggesting the uni-directionality of the slc26a6-mediated HCO_3" transport. When pure pancreatic juice was collected in vivo, neither juice volume nor its pH showed differences between WT and slc26a6 null mice.3. The electrogenic HCO_3^-transport (HCO_3^-conductance) across the apical membrane was demonstrated in luminally-perfused isolated pancreatic ducts as changes in intracellular pH induced by manipulation of bath K^+ concentration in the condition that basolateral HCO_3^-transport was inhibited. The apical HCO_3^- conductance was not dependent on and was abolished in isolated ducts from AF mice. The data suggest that CFTR works as a HCO_3" channel in pancreatic duct cells.

我们用分离自豚鼠和转基因小鼠的小叶间胰管段研究了HCO_3-跨膜转运的分子机制。作为一项临床研究，我们检测了日本人CFTR（囊性纤维化跨膜传导调节因子）的多态性，并建立了一种简单的方法来测量汗液中的浓度.从AF小鼠（引入人类AF 508突变的囊性纤维化模型）分离的胰管具有非常差的cAMP刺激的液体分泌能力和顶端膜的Na^+-H^+交换（NHE）活性。顶端NHE活性的增强可能与降低胰液pH和酸化有关.在slc 26 a6基因敲除小鼠中，[Cl ^-] i/[HCO_3^-] o交换的HCO_3--内流模式显著增加，而[Cl ^-] i/[HCO_3^-] o交换的HCO_3^--外流模式减少，提示slc 26 a6基因敲除小鼠HCO_3--转运的单向性。当在体内收集纯胰液时，无论是汁液体积还是其pH都没有显示WT和slc 26 a6缺失小鼠之间的差异。在腔灌注的离体胰管中，在基底侧HCO_3 ^-转运受到抑制的情况下，通过调节细胞内K^+浓度，可以引起细胞内pH值的变化，从而证实了跨顶膜的生电性HCO_3 ^-转运（HCO_3^-电导）。在AF小鼠的离体导管中，HCO_3^-传导不依赖于并被消除。提示CFTR在胰管细胞中起HCO_3 ~-通道的作用。

项目成果

期刊论文数量（48）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Identification of key residues that cause differential gallbladder response to PACAP and VIP in the guinea pig.

鉴定导致豚鼠胆囊对 PACAP 和 VIP 产生不同反应的关键残基。

DOI：
发表时间：
2007
期刊：
Am J Physiol Gastrointest Liver Physiol 292
影响因子：
0
作者：
Wei M;Fujiki K;Ando E;Zhaug S;Ozaki T;Ishiguro H;Kondo T;Nokihara K;Wray V;Naruse S.
通讯作者：
Naruse S.

A finger sweat chloride test for the detection of a high-risk group of chronic pancreatitis.

用于检测慢性胰腺炎高危人群的指汗氯化物测试。