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Comparative molecular biology of the natriuretic peptide system (Molecular dissection and mechanism of differentiation of chloride cells)

利钠肽系统的比较分子生物学（氯细胞的分子解剖和分化机制）

基本信息

批准号：
09102008
负责人：
HIROSE Shigehisa
金额：
$ 100.86万
依托单位：
Tokyo Institute of Technology
依托单位国家：
日本
项目类别：
Grant-in-Aid for Specially Promoted Research
财政年份：
1997
资助国家：
日本
起止时间：
1997 至 2001
项目状态：
已结题

项目摘要

We used the comparative approach to gain insights into the complex regulatory system of the body fluid homeostasis by using animals with morphological and functional specializations such as the eel that can survive both in freshwater and seawater and the Osorezan dace that can live and grow in a pH 3.5 lake. (1) Through the analyses of both ligands and the corresponding receptors, we showed that the natriuretic peptide (NP) system is a key endocrine system that governs the euryhalinity of eel. NP is not only involved in quick regulation of various pre-existing transporters upon transfer to different salinities, but also stimulates secretion of cortisol and growth hormone, thereby being involved in long-term adaptation. We also identified NPs from diverse vertebrate species that perform unique osmoregulation such as sharks and hagfish to assess molecular evolution of the NP family. (2) Molecular mechanism of acid adaptation of the Osorezan dace was clarified by identifying ion transporters, channel, and their related molecules that become highly induced when dace are transferred from neutral to acidic water. Furthermore, the molecules responsible for the acid tolerance were mainly expressed in chloride cells. (3) Osmoregulation in teleost fish is achieved largely through active salt transport by specialized cells known as chloride cells. Reflecting their extraordinary power of ion transport, chloride cells are rich in Na, K-ATPase. Exploiting this unique property of the chloride cell, we succeeded in identifying a K channel likely to be functionally coupled with Na, K-ATPase ; identification of such a K channel has been a long-standing goal in animal physiology. (4) Autoradiographic localization of eel NP receptor revealed an unexpectedly dense localization in the gill chondrocytes, suggesting tight relationship between the NP system and bone metabolism, which then open a new avenue in the field of bone research.

我们使用比较的方法，以获得深入了解体液稳态的复杂的调节系统，通过使用动物的形态和功能的专业化，如鳗鱼，可以生存在淡水和海水和Osorezan Dace，可以生活和生长在pH值3.5的湖泊。(1)通过对配体和受体的分析，我们发现钠尿肽（NP）系统是调控鳗鱼广盐性的关键内分泌系统。NP不仅参与各种预先存在的转运蛋白在转移到不同盐度时的快速调节，而且还刺激皮质醇和生长激素的分泌，从而参与长期适应。我们还确定了从不同的脊椎动物物种，如鲨鱼和盲鳗，执行独特的神经调节NP评估NP家族的分子进化。(2)通过鉴定离子转运体、通道及其相关分子，阐明了奥索赞鱼从中性水转移到酸性水时高度诱导的酸适应的分子机制。此外，负责耐酸性的分子主要在氯细胞中表达。(3)硬骨鱼的渗透调节主要是通过被称为氯细胞的专门细胞的主动盐运输来实现的。氯细胞富含Na，K-ATP酶，这反映了它们非凡的离子运输能力。利用氯细胞的这种独特性质，我们成功地鉴定了可能与Na，K-ATP酶功能性偶联的K通道;鉴定这样的K通道一直是动物生理学的长期目标。(4)放射自显影定位结果显示，鳗鱼NP受体在鳃软骨细胞中的分布密度很高，提示NP系统与骨代谢密切相关，为骨的研究开辟了一条新的途径。