Renal Proximal tubule

MM Meyer, AS Verkman. Evidence for water channels in renal proximal tubule cell membranes. J Membrane Biol 96 107-119, 1987. 

Takenaka M et al. Isolation of genes identified in mouse renal proximal tubule by comparing different gene expression profiles. Kidney Int 1998 53 562— 572. 

Sweet DH, Miller DS, Pritchard JB. Basolateral localization of organic cation transporter 2 in intact renal proximal tubules. Am J Physiol Renal Physiol 2000 279(5) F826—F834. 

Aleo, M.D., Wyatt, R.D. and Schnellmann, R.G. (1991). The role of altered mitochondrial function in citrinin-induced toxicity to rat renal proximal tubule suspensions. Toxicol. Appl. Pharmacol. 109 455 463. 

Messana, J.M., Cieslinski, D.A., O Connor, R.P. and Humes, H.D. (1988). Glutathione protects against exogenous oxidant injury to rabbit renal proximal tubules. Amer. J. Physiol. 255 F874-F884. 

Tay, L.K., Bregman, D.L., Maters, B.G. and Williams, RD. (1988). Effects of A.s-diaminedi-chloroplatinum (I) on rabbit kidney in vivo and on rabbit renal proximal tubule cells in culture. Cancer Res. 48 2538-2543. 

Ware, R.A., Burkholder, P.M. and Chang, L.W. (1975). Ultrastractural changes in renal proximal tubules after chronic organic and inorganic mercury intoxication. Environ. Res. 10 121-140. 

Masereeuw R, Terlouw SA, van Aubel RA, Russel FG, Miller DS (2000) Endothe-lin B receptor-mediated regulation of ATP-driven drug secretion in renal proximal tubule. Mol Pharmacol 57 59-67... 

Terlouw SA, Masereeuw R, Russel FG, Miller DS (2001) Nephrotoxicants induce endothelin release and signaling in renal proximal tubules Effect on drug efflux. Mol Pharmacol 59 1433-1440... 

Hypocalcemia (below-normal blood calcium) stimulates release of parathyroid hormone (PTH), which in turn binds to receptors on cells of the renal proximal tubules. The receptors are coupled through cAMP to activation of a la-hydroxylase important for the final, rate-hmiting step in the conversion of vitamin D to 1,25-DHCC (dihydroxycholecalciferol or caldtriol). 

Fanconi renal syndrome (renal proximal tubule defect)... 

Fructose is found in honey and fruit and as part of the disaccharide sucrose (common table sugar). Sucrose is hydrolyzed by intestinal brush border sucrase, and the resulting monosaccharides, glucose and fructose, are absorbed into the portal blood. The liver phosphorylates frurtose and cleaves it into glyceraldehyde and DHAP. Smaller amounts are metabolized in renal proximal tubules. The pathway is shown in Figure 1-12-7 important enzymes to remember are ... 

Genetic deficiency of fructokinase is benign and often detected incidentally when the urine is checked for glucose with a dipstick. Fructose 1-phosphate aldolase deficiency is a severe disease because of accumulation of fructose 1-phosphate in the liver and renal proximal tubules. Table 1-12-4 compares the two conditions. Symptoms are reversed after removing fructose and sucrose from the diet. 

The MRL was based on a NOAEL of 26 mg/kg/day in the drinking water for 4 days for hepatic effects in mice (Larson et al. 1994b). The NOAEL of 26.4 mg/kg/day was divided by an uncertainty factor of 100 (10 for extrapolation from animals to humans and 10 for human variability) to arrive at the MRL of 0.3 mg/kg/day. A study performed by Moore et al. (1982) found renal effects in CFLP Swiss mice dosed at 65.5 mg/kg/day by gavage in oil. Another study by Larson et al. (1993) found both hepatic (elevated SDH, ALT and AST, hepatocyte necrosis) and renal (proximal tubule necrosis) lesions in Fischer 344 rats and hepatic lesions only in B6C3Fj mice induced by chloroform administered at 34 mg/kg/day once by gavage in oil. Lesions in the Larson et al. (1993) study were ranked as less serious LOAELs. 

In vitro studies suggest that the GRK4 SNPs impair the function of receptors, increase blood pressure, and impair the diuretic and natriuretic effects of dopamine Dj-like agonist stimulation. Inappropriate desensitization of the dopamine D, receptor in renal proximal tubules in hypertension may result in the decreased ability of the kidney to eliminate a sodium chloride load—a key risk factor in the development of hypertension. 

Miller DS, Sussman CR, Refro JL (1998) Protein kinase C regulation of P- ycoprotein-mediated xenobiotic secretion in renal proximal tubule. Am J Physiol 275 F785-795... 

S-(1,2,3,4,4-pentachloro-1,3-butadienyl)-L-cysteine toxicity to rabbit renal proximal tubules. Toxicol AppI Pharmacol 90 513-521. 

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