Transporters renal

Lisinopril 20-40 mg p.o. qid Oral uptake likely via peptide transport, renal excretion... 

Alterations in organic acid and base transport Renal wasting of potassium, magnesium, and calcium Polyuria... 

Membrane chloride transport (e.g. sodium-dependent transport. Renal brush-border, GABAa receptor),... 

The anticonvulsants primidone and carbamazepine inhibit biotin uptake into brush-border membrane vesicles from human intestine (Zempleni et al. 2009). Long-term therapy with anticonvulsants increases both biotin catabolism and urinary excretion of 3-hydroxyisovaleric acid. These eifects might be due to displacement of biotin from biotinidase by anticonvulsants, thereby aifecting plasma transport, renal handling or cellular uptake of biotin. 

Hydroxy vitamin D pools ia the blood and is transported on DBF to the kidney, where further hydroxylation takes place at C-1 or C-24 ia response to calcium levels. l-Hydroxylation occurs primarily ia the kidney mitochondria and is cataly2ed by a mixed-function monooxygenase with a specific cytochrome P-450 (52,179,180). 1 a- and 24-Hydroxylation of 25-hydroxycholecalciferol has also been shown to take place ia the placenta of pregnant mammals and ia bone cells, as well as ia the epidermis. Low phosphate levels also stimulate 1,25-dihydtoxycholecalciferol production, which ia turn stimulates intestinal calcium as well as phosphoms absorption. It also mobilizes these minerals from bone and decreases their kidney excretion. Together with PTH, calcitriol also stimulates renal reabsorption of the calcium and phosphoms by the proximal tubules (51,141,181—183). 

Fig. 2. Schematic representation of relevant electrolyte transport through the renal tubule, depicting the osmolar gradient ia medullary iaterstitial fluid ia ywOj yW where represents active transport, —passive transport, hoth active and passive transport, and passive transport of H2O ia the presence of ADH, ia A, the cortex, and B, the medulla. An osmole equals a mole of solute divided by the number of ions formed per molecule of the solute. Thus one mole of sodium chloride is equivalent to two osmoles, ie, lAfNaCl = 2 Osm NaCl. ADH = antidiuretic hormone.

The co-administration of drugs which inhibit the transporters involved in renal tubular secretion can reduce the urinaty excretion of drugs which are substrates of the transporter, leading to elevated plasma concentrations of the drugs. For example, probenecid increases the plasma concentration and the duration of effect of penicillin by inhibiting its renal tubular secretion. It also elevates the plasma concentration of methotrexate by the same mechanism, provoking its toxic effects. 

Shitara Y, Sato H, Sugiyama Y (2005) Evaluation of drug-drug interactions in the hepatobiliary and renal transport of drugs. Annu Rev Pharmacol Toxicol 45 689-723... 

Bile ducts Various intravenous cholegraphic agents, e.g., iodipamide Biligrafin Anion transport Lin SK et al (1977) Iodipamide kinetics Capacity-limited biliary excretion with simultaneous pseudo-first-order renal excretion. J Pharm Sci 66 1670-1674... 

In eukaryotes there is also evidence that Met(O) is actively transported. It has been reported that Met(O) is transported into purified rabbit intestinal and renal brush border membrane vesicles by a Met-dependent mechanism and accumulates inside the vesicles against a concentration gradient102. In both types of vesicles the rate of transport is increased with increasing concentrations of Na+ in the incubation medium. The effect of the Na+ is to increase the affinity of Met(O) for the carrier. Similar to that found in the bacterial system, the presence of Met and other amino acids in the incubation medium decreased the transport of Met(O). These results suggest that Met(O) is not transported by a unique carrier. 

Wright SH and Dantzler WH. Molecular and cellular physiology of renal organic cation and anion transport. Physiol Rev 2004 84 987-1049. 

Suhre WM, Ekins S, Chang C, Swaan PW and Wright SH. Molecular determinants of substrate/inhibitor binding to the human and rabbit renal organic cation transporters hOCT2 and rbOCT2. Mol Pharmacol 2005 67 1067-77. 

There are numerous abnormalities of cysteine metabolism. Cystine, lysine, arginine, and ornithine are excreted in cystine-lysinuria (cystinuria), a defect in renal reabsorption. Apart from cystine calculi, cystinuria is benign. The mixed disulfide of L-cysteine and L-homocysteine (Figure 30-9) excreted by cystinuric patients is more soluble than cystine and reduces formation of cystine calculi. Several metabolic defects result in vitamin Bg-responsive or -unresponsive ho-mocystinurias. Defective carrier-mediated transport of cystine results in cystinosis (cystine storage disease) with deposition of cystine crystals in tissues and early mortality from acute renal failure. Despite... 

A number of genetic diseases that result in defects of tryptophan metabolism are associated with the development of pellagra despite an apparently adequate intake of both tryptophan and niacin. Hartnup disease is a rare genetic condition in which there is a defect of the membrane transport mechanism for tryptophan, resulting in large losses due to intestinal malabsorption and failure of the renal resorption mechanism. In carcinoid syndrome there is metastasis of a primary liver tumor of enterochromaffin cells which synthesize 5-hydroxy-tryptamine. Overproduction of 5-hydroxytryptamine may account for as much as 60% of the body s tryptophan metabolism, causing pellagra because of the diversion away from NAD synthesis. 

Igarashi and Aronson [22] found that the renal brush border Na /H exchanger (resistant-type) was inhibited 40% by 1 mM NEM, and inhibition was not blocked by 1 mM amiloride. Haggerty et al. [13] reported that both the apical and basolat-eral Na /H exchangers in LLC-PKi cells were inactivated by 0.5mM NEM, although the apical Na /H exchanger was more sensitive to inhibition (70% inhibition compared to 20% inhibition of the basolateral transport activity). 

Candidates for the renal brush border Na /H exchanger transport protein identified by covalent labeling, affinity chromatography, or other methods... 

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