Proximal Nephron

Abstract

The kidney plays a fundamental role in maintaining body salt and fluid balance and blood pressure homeostasis through the actions of its proximal and distal tubular segments of nephrons. However, proximal tubules are well recognized to exert a more prominent role than distal counterparts. Proximal tubules are responsible for reabsorbing approximately 65% of filtered load and most, if not all, of filtered amino acids, glucose, solutes, and low molecular weight proteins. Proximal tubules also play a key role in regulating acid-base balance by reabsorbing approximately 80% of filtered bicarbonate. The purpose of this review article is to provide a comprehensive overview of new insights and perspectives into current understanding of proximal tubules of nephrons, with an emphasis on the ultrastructure, molecular biology, cellular and integrative physiology, and the underlying signaling transduction mechanisms. The review is divided into three closely related sections. The first section focuses on the classification of nephrons and recent perspectives on the potential role of nephron numbers in human health and diseases. The second section reviews recent research on the structural and biochemical basis of proximal tubular function. The final section provides a comprehensive overview of new insights and perspectives in the physiological regulation of proximal tubular transport by vasoactive hormones. In the latter section, attention is particularly paid to new insights and perspectives learnt from recent cloning of transporters, development of transgenic animals with knockout or knockin of a particular gene of interest, and mapping of signaling pathways using microarrays and/or physiological proteomic approaches.

Prostaglandin E2 increases proximal tubule fluid reabsorption, and modulates cultured proximal tubule cell responses via EP1 and EP4 receptors

“…The majority of PT sodium transport is mediated by the sodium-hydrogen exchanger, NHE1 on the basolateral side and NHE3 on the apical membrane. 28 Unlike the increase in basolateral NaK shown here, NHE1 and NHE3 levels were unchanged following 24 h PGE 2 (unpublished data).…”

Proximal tubule-dominant transfer of AT1a receptors induces blood pressure responses to intracellular angiotensin II in AT1a receptor-deficient mice

“…The proximal tubule is the most important tubular segment in the kidney responsible for the reabsorption of ϳ65% of the filtered sodium and fluid (48). Proximal tubule sodium and fluid reabsorption are regulated by a complexity of hemodynamic (37) and humoral factors, including ANG II, catecholamines (1,21), atrial natriuretic peptide (17,49), and endothelin (18,23).…”

Gastrin decreases Na+,K+-ATPase activity via a PI 3-kinase- and PKC-dependent pathway in human renal proximal tubule cells

“…NHE3 is located at the apical and Na ϩ ,K ϩ -ATPase at the basolateral membrane of the renal proximal tubule and thick ascending limb (31). We now report that Na ϩ ,K ϩ -ATPase is regulated by gastrin in a fashion similar to NHE3, sharing the same pathway, involving PI 3-kinase, PLC, cPKC, and intracellular calcium.…”

“…This process involved both the PI 3-kinase and PKC pathways (16). Sodium reabsorption by the renal proximal tubule depends on multiple sodium transporters and exchangers and pumps, of which the major sodium exchanger is NHE3 located at the apical membrane, whereas sodium inside the cell is pumped out by Na ϩ ,K ϩ -ATPase at the basolateral membrane (31).…”