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 m easured in isolated perfused S-1, S-2, and S-3 segments of the rabbit proxi mal tubule. In lumen-to-bath experiments, the perfusion solution contained 4.6 mu M H-3-GSH with or without 1.0 mM acivicin. In all three segments per fused without acivicin, luminal disappearance rate (J(DL)) and bath appeara nce rate (J(AB)) of H-3-GSH were 14.5 +/- 0.5 and 1.2 +/- 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 H-3-GSH in S-1, S-2, and S-3 seg ments when acivicin was absent were 23.1 +/- 2.0, 31.7 +/- 11.4, and 143.5 +/- 17.9 mu M, respectively. With acivicin in perfusate, cellular concentra tions were reduced but there was no change in the heterogeneity profile. In bath-to-lumen transport experiments (S-2 segments only), the bathing solut ion contained 2.3 mu M H-3-GSH. (3H)-GSH appearance in the lumen (J(AL) fmo l/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 +/- 10 and 6.1 +/- 0.5 mu M, 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) t he S-3 segment has the greatest GSH cellular concentration because its baso lateral membrane has less capacity for cell-to-bath transport of GSH; and ( 4) GSH can be secreted intact from the peritubular compartment into the tub ular lumen.