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Concerted mechanisms of transporters for exocrine secretion

外分泌转运蛋白的协同机制

基本信息

批准号：
07044298
负责人：
MURAKAMI Masataka
金额：
$ 7.55万
依托单位：
Okazaki Research Institutes, National Institute for Physiological Sciences
依托单位国家：
日本
项目类别：
Grant-in-Aid for international Scientific Research
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

项目摘要

The project aims to study a co-operative mechanism of the transporter proteins (channel, cotransport, antiport & pumps) to produce a macroscopic secretion (concerted mechanism) in the exocrine acinar cells. The project focuses on transport ability, energy supply and its control of transporter proteins in the salivary gland. Collaborative laboratories, using different specialized techniques, measured water & electrolyte movements across cell membranes and intracellular information system in the isolated cells and the vascularly perfused whole gland. NIPS group developed a technique to isolate and perfuse the parotid gland. They measured fluid secretion and oxygen consumption simultaneously, and assessed contribution of Na-dependent transporters to organized secretion. Manchester/Okazaki team measured cell volume change in the whole gland and isolated cells using pulse gradient NMR and fluorometry. They found positive relationship between intracellular Cl and cell volume. Matsudo team fo … More und an activity of NOS involving cGMP accumulation in the rabbit parotid gland. They also identified VAMP-2 as a exocytosis-related protein in the vesicle membrane. Copenhagen team measured inositol compounds along the time course of secretion, and found that activation of purinergic receptor inhibit mobilization of IP3 by substance P.NIPS/Harvard team supported experimentally by observation that ATP inhibits fluid secretion by ACh. Harverd team found that CCh and substance P caused phosphorylation of PKC delta as early event, then MAP kinase was activated. Sydney group examined mechanism of ductal K secretion and Na reabsorption. They concluded no contribution of Na/K/2Cl cotransport for ductal K secretion in the mouse, and found involvement of G-protein on NaCl reabsorption in the duct. NIH group examined activation mechanism of Na/K/2Cl cotransporter at molecular level, and found a possible role of cotransporter to excrete ammonium physiologically from saliva. Kitasato/Cagliari team observed 3D structure of intercellular path and exocytosis, and found functional difference in the exocytosis-endocytosis coupling via microfilament between CCh and isoproterenol stimulation. The collaboration allowed to use the same preparation technique of the materials and quite different measurement techniques used by each laboratories, so substantial synergetic results was produced. Less

该项目旨在研究转运蛋白（通道，共转运，反向转运和泵）的合作机制，以在外分泌腺泡细胞中产生宏观分泌（协调机制）。该项目的重点是运输能力，能量供应及其控制的转运蛋白在唾液腺。合作实验室，使用不同的专业技术，测量了水和电解质运动在细胞膜和细胞内信息系统在分离的细胞和血管灌注的整个腺体。NIPS组建立了腮腺的分离和灌注技术。他们同时测量液体分泌和氧消耗，并评估Na依赖性转运蛋白对组织分泌的贡献。Manchester/Okazaki团队使用脉冲梯度NMR和荧光测定法测量了整个腺体和分离细胞的细胞体积变化。他们发现细胞内Cl与细胞体积呈正相关。松户队 ...更多信息和NOS的活性，涉及cGMP的积累在兔腮腺。他们还将VAMP-2鉴定为囊泡膜中的胞吐相关蛋白。哥本哈根团队测量肌醇化合物沿着分泌的时间过程，发现嘌呤能受体的激活抑制P物质对IP 3的动员。NIPS/哈佛团队通过观察ATP抑制ACh分泌的实验支持。Harverd等发现CCh和P物质可引起PKC δ磷酸化，从而激活MAP激酶。Sydney组检测导管K分泌和Na重吸收机制。他们得出结论，Na/K/2Cl共转运对小鼠导管中的K分泌没有贡献，并且发现G蛋白参与导管中的NaCl重吸收。NIH小组从分子水平研究了Na/K/2Cl协同转运蛋白的激活机制，发现协同转运蛋白可能在生理性地从唾液中排泄铵中起作用。Kitasato/卡利亚里团队观察了细胞间通路和胞吐作用的三维结构，发现CCh和异丙肾上腺素刺激之间通过微丝的胞吐-胞吞偶联的功能差异。这种合作允许使用相同的材料制备技术和每个实验室使用的非常不同的测量技术，因此产生了实质性的协同效应。少