DEVELOPMENT OF RENAL AMINO ACID TRANSPORT

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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.