DEVELOPMENT OF RENAL AMINO ACID TRANSPORT

肾小管吸收能力减弱，这是 未成熟的肾脏导致“生理性氨基酸尿症” 鼠、狗和人出生后的早期阶段。成人肾脏类型 随着新生儿的成熟，氨基酸的重吸收逐渐实现。 尽管导致运输成熟的机制仍然是 发现，可能会随着年龄的增长而发生变化，这会影响 肾氨基酸的载体(S)的作用 酸运输。这可能是细胞改变的结果。 膜功能与之相连的代谢或发育的代谢 膜结构或成分的变化。运输成熟度是 与显著的肾脏发育相平行，并可能部分归因于 导致两者表面积增加的形态变化 肾脏溶质转运所通过的刷缘和基侧膜 发生。 体外研究表明，肾脏的氨基酸转运模式发生了变化。 皮质切片、孤立的肾近端小管和肾刷缘 胎膜，比较新生儿和成人。要了解这些问题的本质 与年龄相关的改变，溶质通过肾刷状边界和 将研究来自不同年龄动物的基底外侧小泡，以及 已知的肾脏溶质调节剂--ATP、NAD、NADH和cAMP的影响 运输，将被审查。这些物质的物理化学特性 膜的建立将通过测定膜的流动性、脂质 组成，以及蛋白质的磷酸化程度受 三磷酸腺苷和营地。在这些特征中发现的年龄相关差异可能 使我们更好地理解导致 肾运输过程的个体发育。此外，交通方面的知识 新生儿肾小管细胞内发生的导致氨基酸减少的事件 重吸收也有助于解释遗传性运输的病因。 针对这些异常的动物模型很少，而且有限 受影响的人的调查程序。

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.