Luminal and basolateral membrane transport of glutathione in isolated perfused S(1), S(2), and S(3) segments of the rabbit proximal tubule.
Lumen-to-bath and bath-to-lumen transport rates of glutathione (GSH) were measured in isolated perfused S(1), S(2), and S(3) segments of the rabbit proximal tubule. In lumen-to-bath experiments, the perfusion solution contained 4.6 microM (3)H-GSH with or without 1.0 mM acivicin. In all three segments perfused without acivicin, luminal disappearance rate (J(DL)) and bath appearance rate (J(AB)) of (3)H-GSH were 14.5 +/- 0.5 and 2.2 +/- 0.8 fmol/min per mm tubule length, respectively. With acivicin present, J(DL) and J(AB) were reduced to 1.3 +/- 0.4 and 0.5 +/- 0.3, respectively, with no differences among segments. Cellular concentrations of (3)H-GSH in S(1), S(2), and S(3) segments when acivicin was absent were 23.1 +/- 2.0, 31.7 +/- 11.4, and 143.5 +/- 17.9 microM, respectively. With acivicin in perfusate, cellular concentrations were reduced but there was no change in the heterogeneity profile. In bath-to-lumen transport experiments (S(2) segments only), the bathing solution contained 2.3 microM (3)H-GSH. (3)H-GSH appearance in the lumen (J(AL), fmol/min per mm) and cellular accumulation from the bath were studied with and without acivicin in the perfusate. J(AL) values were 3.0 +/- 0.2 and 0.2 +/- 0.03 while cellular concentrations were 9.5 +/- 1.0 and 6.1 +/- 0.5 microM, respectively. It is concluded that: (1) GSH is primarily removed from the luminal fluid after degradation to glycine, cysteine, and glutamate, which are absorbed; (2) GSH can be absorbed intact at the luminal membrane; (3) the S(3) segment has the greatest GSH cellular concentration because its basolateral membrane has less capacity for cell-to-bath transport of GSH; and (4) GSH can be secreted intact from the peritubular compartment into the tubular lumen.[1]References
- Luminal and basolateral membrane transport of glutathione in isolated perfused S(1), S(2), and S(3) segments of the rabbit proximal tubule. Parks, L.D., Zalups, R.K., Barfuss, D.W. J. Am. Soc. Nephrol. (2000) [Pubmed]
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