Proximal convoluted tubule, transport mechanisms

RJ Alpern. (1985). Mechanism of basolateralmembrane II -OH /IICOL transport in the rat proximal convoluted tubule. A sodium-coupled electrogenic process. J Gen Physiol 86 613-636. 

The exact mechanism(s) responsible for fluoride s nephrotoxicity remain to be defined. The fluoride ion interferes with normal cell function on several levels. Fluoride is an inhibitor of several cellular enzyme systems and dirninishes tissue respiration and anaerobic glycolysis [89]. In the kidney, fluoride interferes with transport of sodium in the proximal convoluted tubule. It also inhibits adenylate cyclase in the collecting system and dirninishes the action of antidiuretic hormone. Experimental evidence in rats indicates that the chloride dependent pump, in the thick ascending part of Henle s loop, also is inhibited [90]. In human collecting duct cell cultures, exposure to fluoride ions inhib-... 

Tubular secretion of drugs occurs in the proximal convoluted tubule by active transport mechanisms normally used for the removal of waste products. Transport systems exist for the secretion of acidic substances, for example uric acid and basic substances, for example creatinine. Many drugs can be actively secreted by this mechanism, which increases their rate of removal from the body. 

Renal proximal tubular epithelium (e.g., convoluted tubules) reclaim protein, including immunoglobulin, from the urinary filtrate via sorting/recy-cling mechanisms in intracellular vesicles. The apical (lumen-facing) surface of these cells features a specialized brush border which expresses FcRn closely associated with (S2-microglobulin [110,116], Studies with cultured human renal proximal tubular epithelial cells have demonstrated bidirectional IgG transport and salvage by fully functional FcRn [110] as discussed further in the next section. 

Figure 10.1 Sites and mechanisms of action of diuretics. The location of each cell type along the nephron is indicated by the shading patterns. Spironoiactone (not shown) is a competitive aldosterone antagonist and acts primarily in the collecting duct. PT, proximal tubule LH, loop of Henie TAL, thick ascending limb DT, distal tubule DCT, distal convoluted tubule CD, collecting duct PC, principal cell CA, carbonic anhydrase CAI, carbonic anhydrase inhibitors , primary active transport. (Adapted with permission from Ellison D H 1991 The physiologic basis of diuretic synergism its role in treating diuretic resistance. Annals of Internal Medicine 114 886-894.)...

To understand the mechanism of urine concentration, one must retrace the fate of the fluid in the various segments of the kidney. In the glomerulus, the membranes of the Bowman s capsule cells allow passage of all plasma components except protein. The ultrafiltrate is markedly reduced in volume as it passes through the proximal tubule. In fact, only 20% of the original volume reaches the distal portion of the proximal convoluted tube. The volume of the ultrafiltrate is reduced due to passive water reabsorption. Passive means that no known molecular mechanism exists for the transport of water from the lumen of the proximal tubule to the interstitial tissue. However, the movement of water follows that of sodium. In the proximal tubule, sodium is excreted actively into the interstitial tissue, and as a result, the osmotic pressure of the interstitial tissues increases. This draws water from the lumen of the tubule into the interstitial environment of the medulla because the tubule is highly permeable to water. 

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