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J Am Soc Nephrol 11:1008-1015, 2000
© 2000 American Society of Nephrology

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Luminal and Basolateral Membrane Transport of Glutathione in Isolated Perfused S1, S2, and S3 Segments of the Rabbit Proximal Tubule

LISA D. PARKS*, RUDOLFS K. ZALUPS{dagger} and DELON W. BARFUSS*

* Biology Department, Georgia State University, Atlanta, Georgia
{dagger} Division of Basic Medical Sciences, Mercer University School of Medicine, Macon, Georgia.

Correspondence to Dr. Delon W. Barfuss, Biology Department, Georgia State University, Atlanta, GA 30302-4010. Phone: 404-651-3081; Fax: 404-651-2509; E-mail: biodwb{at}panther.gsu.edu

Abstract. Lumen-to-bath and bath-to-lumen transport rates of glutathione (GSH) were measured in isolated perfused S1, S2, and S3 segments of the rabbit proximal tubule. In lumen-to-bath experiments, the perfusion solution contained 4.6 µM 3H-GSH with or without 1.0 mM acivicin. In all three segments perfused without acivicin, luminal disappearance rate (JDL) and bath appearance rate (JAB) of 3H-GSH were 14.5 ± 0.5 and 2.2 ± 0.8 fmol/min per mm tubule length, respectively. With acivicin present, JDL and JAB were reduced to 1.3 ± 0.4 and 0.5 ± 0.3, respectively, with no differences among segments. Cellular concentrations of 3H-GSH in S1, S2, and S3 segments when acivicin was absent were 23.1 ± 2.0, 31.7 ± 11.4, and 143.5 ± 17.9 µM, respectively. With acivicin in perfusate, cellular concentrations were reduced but there was no change in the heterogeneity profile. In bath-to-lumen transport experiments (S2 segments only), the bathing solution contained 2.3 µM 3H-GSH. 3H-GSH appearance in the lumen (JAL, fmol/min per mm) and cellular accumulation from the bath were studied with and without acivicin in the perfusate. JAL values were 3.0 ± 0.2 and 0.2 ± 0.03 while cellular concentrations were 9.5 ± 1.0 and 6.1 ± 0.5 µM, 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 S3 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.






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