Renal glutathione transport. Characteristics of the sodium-dependent system in the basal-lateral membrane.
Na+-dependent GSH transport in basal-lateral membrane vesicles from rat kidney exhibited saturation kinetics while Na+-independent flux increased linearly up to 10 mM GSH. Inhibitor studies showed that GSH transport was not dependent upon the catalytic activity of gamma-glutamyltransferase. K+, choline and NH+4 ions did not stimulate GSH transport, but Li+ partially substituted for Na+. Na+-dependent GSH transport was inhibited by other gamma-glutamyl amino acids. The membrane also showed Na+-dependent transport of glutathione disulfide (GSSG) and gamma-glutamylglutamate. These results show that specificity resides in the gamma-glutamyl moiety and suggest that this system may be a general transport system for gamma-glutamyl compounds. Results from four types of experiments showed that Na+-dependent GSH transport was electrogenic. Transport was stimulated by negative and inhibited by positive valinomycin-induced K+ diffusion potentials; the transport rate was influenced by the anion component of the Na+ salt in the order NaSCN greater than NaCl greater than Na2SO4; analysis of the Na+ concentration dependence indicated coupling of at least 2 Na+/GSH; comparison of GSH-dependent Na+ transport and Na+-dependent GSH transport gave a Na+:GSH stoichiometry of 2:1. Thus, energy is coupled to the transport of GSH in the form of the cellular Na+ gradient and the membrane potential. This system, if it functions in vivo, can act as a mechanism for extraction of GSH from the renal circulation.
D000596:Amino Acids / Q000494:pharmacology; D000818:Animals; D001692:Biological Transport / Q000187:drug effects; D002462:Cell Membrane / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D007668:Kidney / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008564:Membrane Potentials; D009842:Oligopeptides / Q000494:pharmacology; D011339:Probenecid / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology*; D013379:Substrate Specificity
D000596:Amino Acids; D009842:Oligopeptides; D012964:Sodium; D005978:Glutathione; D011339:Probenecid