Heterogeneity of glutathione synthesis and secretion in the proximal tubule of the rabbit.

Abstract

This study was designed to examine the synthesis and possible secretion of glutathione (GSH) in the S1, S2, and S3 segments of the rabbit proximal tubule. GSH synthesis and secretion rates were measured in the three segments of the proximal tubule, using the isolated perfused renal tubule technique. Tritiated (3H) glycine was perfused into segments and synthesized [3H]GSH (3H on the glycine residue) was measured in the bathing solution, collectate, and tubule extract. In the S1 segments, GSH was synthesized at the rate of 8.65 +/- 0.88 fmol.min-1.mm-1 tubule length and preferentially secreted into the lumen at the rate of 7.28 +/- 0.74 fmol.min-1.mm-1. The difference between synthesis and secretion appeared in the bathing solution. The S2 segment synthesized GSH at the rate of 3.88 +/- 0.82 and secreted GSH at the rate of 2.78 +/- 0.57 fmol.min-1.mm-1. GSH synthesis and secretion rates in the S3 segment were 5.45 +/- 1.19 and 4.22 +/- 1.16 fmol.min-1.mm-1, respectively. Cellular concentrations of [3H]GSH increased along the length of the proximal tubule, with the highest concentrations in the S3 segment. The respective GSH cellular concentrations in the S1, S2, and S3 segments were 35.89 +/- 10.51, 49.65 +/- 9.32, and 116.90 +/- 15.76 microM. These findings indicate that there is heterogeneity of GSH synthesis along the proximal tubule and that synthesized GSH is secreted preferentially into the lumen.