Evidence for the renal paratubular transport of glutathione

Abstract

The catabolism of glutathione in various nonrenal tissues occurs through an interorgan process [ 1,2]. For example, the turnover of glutathione within rat liver is initiated by the unidirectional release of glutathione to the blood plasma [3]. The released glutathione is carried to the kidney where it is nearly quantitatively extracted and degraded to its constituent amino acids [4,5]. The glutathionemia and the pronounced glutathionuria observed in a patient who lacks detectable -r-glutamyltranspeptidase [6] and in mice treated with inhibitors of y-glutamyltranspeptidase [7,8] indicate that this enzyme catalyzes the initial reaction in glutathione catabolism. The transpeptidase is an amphipathic membrane glycoprotein [9] that is found to the greatest extent in the kidney. Within this tissue, the enzyme is primarily associated with the brush border membrane of the proximal tubule cells [lo], where it is asymmetrically orientated on the lumenal surface [ 111. the glomeruli even when the arterial glutathione concentration is increased to a value 200-fold greater than normal [5]. Therefore, the kidney may contain a mechanism for the transport of glutathione across the basolateral plasma membrane. However, small amounts of y-glutamyltranspeptidase may be associated with the glomeruli [13], with the renal microvasculature [14], or with the basolateral membrane of the proximal tubule [ 151. Thus, the apparent extraction of glutathione by the kidney may be due to its catabolism within the post-glomerular paratubular space. In order to resolve these two possibilities, we have used the procedures in [16] to study the renal paratubular handling of glutathione.