Proximal Tubular Cells and their Functions

The proximal tubular cell plays a major role in the elimination of both inorganic and organic substrates. The ceUs have two distinct membrane domains. The basolateral membrane is in contact with the blood, and the apical brush-border membrane lines the tubular lumen. 

Methods of traversing the basolateral membrane include uptake systems for organic cations and anions via fadhtated diffusion and/or active transport [1]. Organic anions and cations cross the basolateral membrane via ATP-driven or secondary active processes (H -antiport) [2]. Basolateral uptake processes include the gamma-glutamyl transport system [3] and those for glycoproteins [4]. Certain proteins (insulin, epidermal growth factor (EGF)) are transcytosed across the tubular cells from the blood to the tubular lumen via receptor-mediated uptake [5]. 

In healthy individuals, useful endogenous compounds that are freely filtered by the glomerulus, only appear in the urine in small quantities. These compounds are rescued by tubular reabsorption. These rescue mechanisms consist of a variety of, mostly, carrier-mediated processes at the luminal site of the tubular cell. Substances transported by reabsorptive systems include sugars [6], amino acids [7], dipeptides [8], urate [9], folate [10], nucleosides [11] and proteins [12]. 

For exogenous compounds such as drugs, various enzymes involved in both phase I and phase II metabolic routes are present, e.g. various isoforms of cytochrome p450, cytochrome b5, glucuronyl transferase and sulfotransferase [15]. 

In addition, renal tubular cells contain various proteases for the degradation of proteins and oligopeptides. These enzymes are located predominantly in the lysosomes and micro-somes of these cells, but some have been reported on the brush-border membranes [16]. Degradative enzymes include various endopeptidases, exopeptidases and esterases [17]. 

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