Mechanism of renal peritubular extraction of plasma glutathione

Abstract

To clarify the peritubular mechanism for renal handling of plasma glutathione (GSH), variation of GSH levels in plasma, urine, kidney and liver was examined after intravenous administration of GSH to three groups of animals: control, acivicin-treated and rats treated with buthionine sulfoximine (BSO). Treatment of animals with BSO, a potent inhibitor of de novo GSH synthesis, markedly reduced hepatorenal GSH levels. Acivicin did not affect these levels. Upon intravenous injection of GSH (0.1 mmol/kg), renal GSH levels did not appreciably change in any of three animal groups. The rate of GSH disappearance from the circulation was rapid in control and BSO-treated rats, while it was markedly retarded in animals whose renal .gamma.-glutamyltransferase was extensively inactivated by acivicin. At 30 min after administration a significant amount of injected GSH was localized extracellularly (urine and plasma) in acivicin-treated animals. By contrast, most of the GSH rapidly disappeared from the extracellular space in control and BSO-treated animals. Together with the immunocytochemical evidence for the peritubular .gamma.-glutamyltransferase [Spater, H. W., Poruchynsky, M. S., Quintana, N., Inoue, M. and Novikoff, A. B. (1982) Proc. Natl. Acad. Sci. USA 79, 3547-3550] the present results are fully consistent with the contention that the catalytic function of this enzyme is principally responsible for the peritubular mechanisms for the renal handling of plasma GSH.