Cystine Fluxes Across the Isolated Jejunal Epithelium in Cystinuria: Increased Efflux Permeability at the Luminal Membrane

Abstract

ABSTRACT. In cystinuria, renal clearance of cystine frequently exceeds creatinine clearance, suggesting net cystine secretion; and absorption of the (di)basic amino acid is impaired at the luminal membrane of the jejunal and probably also renal tubular epithelium. We studied cystine transport in vitro in jejunal biopsy specimens of eight subjects with homozygous cystinuria and in 12 controls. Cellular/medium cystine distribution ratio was reduced in cystinuria (1.36 f 0.36 versus 5.36 f 0.61, p < 0.001).Cystine influx across the luminal membrane was normal (221 f 48 versus 261 + 79 pmol. h-' ~m -~) .Measurement of transepithelial cystine fluxes showed net absorption in controls but secretion in cystinuria. Apparent permeability coefficients were close to normal in cystinuria except that the efflux permeability at the luminal membrane was significantly increased (0.839 + 0.22 versus 0.186 2 0.12. h-' ~m -~) , and, accordingly, at the luminal membrane, the influx over efflux permeability ratio was small (1.01 f 0.50 versus 4.95 + 0.80, p < 0.001). The defect in cystine transport in cystinuria is apparently not caused by decreased influx but increased efflux of cystine (or cysteine) from the cell to the lumen across the luminal membrane. (Pediatr Res 21: 477-481, 1987) Abbreviations J, flux of cystine across a membrane m, mucosal or luminal compartment c, cellular compartment S, "serosal" or blood compartment Jmc, flux of cystine from mucosal to cell compartment P, permeability PEG, polyethylene glycol PD, potential difference Isc, short-circuit current GFR, glomerular filtration rate Cystinuria is characterized by increased urinary excretion of cystine and the basic amino acids lysine, arginine, and ornithine and by a tendency to form renal cystine stones (1-3). The amino acid transport defect, present in the mucosa of renal tubuli and small intestine, has been explained either by defective absorption or increased secretion of the amino acids or both (2, 4-9).Amino acids and sodium are cotransported through the luminal membrane of the epithelial cells in proximal tubule and jejunum leading to intracellular accumulation of the amino acids

Regulation ofl-Cystine Transport and Intracellular GSH Level by a Nitric Oxide Donor in Primary Cultured Rabbit Conjunctival Epithelial Cell Layers

“…Such studies are likely to substantiate our present findings. Our results on kinetic parameters and net absorption of L-cystine are similar to those reported for the L-cystine transport processes in a mouse brain endothelial cell line, 30 luminal membrane of jejunal epithelial cells, 31 and renal tubular cells. 32 Apically, L-cystine may be formed from cysteine produced from the hydrolysis of GSH released from cells by the ectoenzyme GGT.…”

Cystine Stones: The Efficacy of Percutaneous and Shock Wave Lithotripsy

“…It is due to a transport defect of amino acids across the luminal membrane of the jejunum and in the renal epithelium [3]. The disease cannot be detected clinically unless a great excretion of cystine and urinary hypersatu ration is presented due to urinary tract stones, a condition that is almost always found in homozygotes, while rarely found in heterozygotes [4,5].…”