Kidneys proximal tubule

Schaub TP, Kartenbeck J, Konig J, Spring H, Dorsam J, Staehler G et al. Expression of the MRP2 gene-encoded conjugate export pump in human kidney proximal tubules and in renal cell carcinoma. J Am Soc Nephrol 1999 10(6) 1159—1169. 

Hatzinger, P.B. and Stevens, J.L. (1989). Rat kidney proximal tubule cells in defined medium the roles of cholera toxin, extracellular calcium and serum in cell growth and expression of y-glutamyltransferase. In Vitro Cell. Dev. Biol. 25(2) 205-212. 

Yang, I.S., Goldinger, J.M., Flong, S.K. and Taub, M. (1988). Preparation of basolateral membranes that transport p-aminohippurate from primary cultures of rabbit kidney proximal tubule cells. J. Cell. Physicol. 135 481-487. 

Zhang, G. and Stevens, J.L. (1989). Tansport and activation of 5-(l, 2-dichlorovinyl)-L-cysteine andA-acetyl-S-(l,2-dichlorovinyl)-L-cysteine in rat kidney proximal tubules. Toxicol. Appl. Pharmacol. 100 51-61. 

As mentioned above, impaired fluid absorption in kidney proximal tubule in AQPl deficiency indicates the need for high cell membrane water permeability for rapid, near-isosmolar fluid transport. The involvement of AQPs in fluid secretion by glands (salivary, submucosal, sweat, lacrimal), and by the choroid plexus and the ciliary body has been investigated using appropriate knockout mouse models. The general conclusion is that AQPs facilitate active fluid (secretion and absorption) when sufficiently rapid, in which case AQP deletion is associated with reduced volume and increased ion/solute content of secreted fluid. AQPs appear not to be needed when fluid secretion rate (per unit epithelial surface area) is low, as AQP-independent water permeability is high enough to support slow fluid secretion (or absorption). 

Van Aubel RA, Smeets PH, Peters JG, Bindels RJ, Russel FG. The MRP4/ ABCC4 gene encodes a novel apical organic anion transporter in human kidney proximal tubules putative efflux pump for urinary cAMP and cGMP. J Am Soc Nephrol 2002 13 595-603. 

Three other forms of the Na+/H+ exchanger have subsequently been cloned. Screening of a rabbit kidney proximal tubule library with an NHE-1 probe (using low stringency hybridization) has led to the identification of two other forms of Na+/H+ exchanger (Tse et al., 1992) that are entirely (NHE-3) or predominantly (NHE-2) expressed in the intestine and kidney. A fourth form of Na+/H+ exchanger (NHE-4) has been identified in the gastrointestinal tract (Orlowski et al., 1992). These isoforms are less sensitive than NHE-1 to amiloride derivatives. 

Zhang, X., Hartz, P.A., Philip, E., Racusen, L.C., and Majerus, P.W., 1998, Cell lines from kidney proximal tubules of a patient with Lowe syndrome lack OCRL inositol polyphosphate 5-phosphatase and accumulate phosphatidylinositol 4,5-bisphosphate. J. Biol. Chem. 273 1574-1582. 

Brunskill NJ, Stuart J, Tobin AB, Walls J, Nahorski S. Receptor-mediated endocytosis of albumin by kidney proximal tubule cells is regulated by phosphatidylinositide 3-kinase. J. Clin. Invest. 1998 101 2140-2150. 

Huls M, Brown CD, Windass AS, Sayer R, van den Heuvel JJ, Heemskerk S, Russel FG, Masereeuw R.The breast cancer resistance protein transporter ABCG2 is expressed in the human kidney proximal tubule apical membrane. Kidney int 2007 73 220-225. Miller DS, Stewart DE, Pritchard JB. Intracellular compartmentation of organic anions within renal cells. Am J Physiol 1993 264 ... 

Sugawara-Yokoo M, Urakami Y, Koyama H, Fujikura K, Masuda S, Saito H, NaruseT, Inui K,Takata K. Differential localization of organic cation transporters rOCTI and rOCT2in the basolateral membrane of rat kidney proximal tubules. Histochem Cell Biol 2000 114 175-180. 

Brandle E,Greven J. Transport ofcimetidine across the basolateral membraneof rabbit kidney proximal tubules interaction with organic anions. Pharmacology 1992 45 231 -240. 

Nielsen R, BIrn H, Moestrup SK, Nielsen M, Verroust P, and Christensen El. Characterization of a kidney proximal tubule cell line, LLC-PKl, expressing endocytotic active megalln. J Am Soc Nephrol 9 1767-1776,1998. 

Birn H, Vorum H, Verroust PJ, Moestrup SK, Christensen El, Receptor- associated protein is important for normal processing of megalin in kidney proximal tubules, J Am Soc Nephrol, 2000 11 191-202. 

Giurgea-Marin L,Toubeau G, Laurent G, Heuson-Stiennon JA,Tulkens PM, Impairment of lysosome-pinocytotic vesicle fusion in rat kidney proximal tubules after treatment with gentamicin at low doses, Toxicol AppI Pharmacol, 1986,86 271-85. 

Foscarnet competitively inhibits Na -Pj cotransport in animal and human kidney proximal tubule brush border membrane vesicles, reversibly inhibiting sodium-dependent phosphate transport [48, 49]. Renal cortical Na-K-ATPase and alkaline phosphatase activity are not inhibited by foscarnet, nor is proline, glucose, succinate, or Na" transport [48,49]. Foscarnet induces isolated phosphaturia without hypophosphatemia in thyroparathyroidectomized rats maintained on a low phosphorus diet, without affecting glomerular filtration rate, urinary adenosine 3 5 -cyclic monophosphate (cAMP) activity, or urinary calcium, sodium or potassium excretion [48,50]. Sodium-Pj cotransport in brush border membrane vesicles from human renal cortex was reported to be even more sensitive to inhibition by foscarnet than in rat renal brush border membrane vesicles [49]. 

Perez M, Castilla M, Torres AM, Lazaro JA, Sarmiento E,Tejedor A. Inhibition of brush border dipeptidase with cilastatin reduces toxic accumulation of cyclosporin Ain kidney proximal tubule epithelial cells. Nephrol Dial Transplant 2004 19 2445-2455. Burdmann EA, Andoh TF, Rosen S, Lindsley J, Munar MY, Elzinga LW, Bennett WM. Experimental nephrotoxicity, hepatotoxicity and pharmacokinetics of cyclosporin G versus cyclosporin A. Kidney Int 1994 45 684-691. 

The red blood cell, which is a convenient model, shows a cell-to-plasma lithium ratio of 0.3-0.6, whereas the Nernst equation would predict a 1.6 ratio. When red blood cells are loaded with hthium in vitro its extrusion is accomplished by a Na /LP countertransporter (SLC), the physiological role of which is unclear, but some believe it represents a mode of operation of the Na /H exchanger. Interestingly, a recent paper suggested that red cell SLC may be a marker of the activity of Na /H exchanger-3 the isoform expressed in the kidney proximal tubule rather than the ubiquitous Na /H exchanger-1 isoform [5]. 

Fowler BA. The morphologic effects of dieldrin and methyl mercuric chloride on pars recta segments of rat kidney proximal tubules. Am J Pathol 1972 69 163-74. 

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