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DEVELOPMENT OF RENAL AMINO ACID TRANSPORT

肾脏氨基酸运输的发展

基本信息

批准号：
3154063
负责人：
MARVIN S MEDOW
金额：
$ 7.39万
依托单位：
NEW YORK MEDICAL COLLEGE
依托单位国家：
美国
项目类别：
财政年份：
1984
资助国家：
美国
起止时间：
1984-09-30 至 1987-08-31
项目状态：
已结题

来源：
https://reporter.nih.gov/project-details/3154063
关键词：
aminoacid transport growth /development renal tubular transport

项目摘要

The diminished renal tubule absorptive capacity which is a hallmark of the immature kidney results in the "physiological aminoaciduria" observed in the early postnatal period of rat, dog and man. Adult patterns of renal amino acid reabsorption are gradually achieved as the neonate matures. Although the mechanisms which result in transport maturation remain to be identified, it is possible that changes may occur with age which influence the function of the carrier(s) responsible for the majority of renal amino acid transport. This may be the result of alterations of cellular metabolism to which membrane function is coupled or of developmental variations in membrane structure or composition. Transport maturation is paralleled by, and may in part be due to, significant renal developmental morphological changes which result in increased surface area of both the brushborder and basolateral membranes across which renal solute transport occurs. Altered patterns of amino acid transport have been shown in vitro in renal cortical slices, isolated renal proximal tubules and renal brushborder membranes, comparing newborn to adult. To understand the nature of these age related alterations, solute transport by renal brushborder and basolateral vesicles from animals of various ages will be studied, and the influence of ATP, NAD, NADH and cAMP, known modulators of renal solute transport, will be examined. Physical-chemical characteristics of these membranes will be established by determining membrane fluidity, lipid composition, and the degree of protein phosphorylation as influenced by ATP and cAMP. Age related differences found in these characteristics may lead to a better understanding of the mechanisms which result in the ontogeny of renal transport process. In addition, knowledge of transport events in the newborn renal tubule cell leading to decreased amino acid reabsorption may also help explain the etiology of inherited transport abnormalities for which there are very few animal models and limited investigative procedures in the affected human.

肾小管吸收能力的降低，这是未成熟的肾脏导致在肾脏中观察到的“生理性氨基酸尿症”。大鼠、狗和人出生后早期肾脏随着新生儿的成熟，氨基酸的重吸收逐渐实现。虽然导致运输成熟的机制仍然是确定，有可能随着年龄的增长而发生变化，负责大部分肾脏氨基的载体的功能酸运输这可能是由于细胞的变化，与膜功能偶联的代谢或发育的代谢膜结构或组成的变化。运输成熟是这可能是由于，部分原因是，形态学变化，导致表面积增加，肾溶质转运的刷状缘和基底外侧膜发生。在体外肾脏移植中，皮质切片、离体肾近端小管和肾刷状缘膜，比较新生儿和成人。为了理解这些的本质，年龄相关改变，肾刷状缘溶质转运，将研究来自不同年龄动物的基底外侧囊泡，已知肾溶质调节剂ATP、NAD、NADH和cAMP的影响运输，将进行检查。这些物质的物理化学特性膜将通过测定膜流动性、脂质组成，以及蛋白质磷酸化程度的影响， ATP和cAMP。在这些特征中发现的年龄相关差异可能导致更好地理解导致肾脏转运过程的个体发生。此外，运输知识新生儿肾小管细胞中的事件导致氨基酸减少重吸收也可能有助于解释遗传性转运的病因这些异常的动物模型非常少，受影响的人的调查程序。