GLUTATHIONE TRANSPORT-SYSTEM IN HUMAN SMALL-INTESTINE EPITHELIAL-CELLS

The present study characterizes for the first time a GSH specific tran sporter in a human intestinal epithelial cell line (1407). GSH metabol ism is very important for the antioxidant and detoxifying action of in testine and for the maintenance of the luminal thiol-disulfide ratio i nvolved in regulation mechanisms of the protein activity of epithelial cells. GSH level decreases have been related to physio-pathological a lterations either of intestine or other organs. GSH specific transport systems have been identified in membranes of various cell types of ra t, mice and rabbit. The presence of a Na+-independent transport system of GSH is confirmed by the similar behaviour of GSH uptake time-cours es when Na+ in extracellular uptake medium was replaced with choline() or K+ as well as by kinetic saturation and by the trans-stimulation effect on GSH uptake in GSH preloaded cells. Moreover, this transporte r is activated when cations are present in extracellular medium and it is affected by membrane potential changes with an increase in GSH upt ake values when membrane depolarization occurs. The present results al so show a remarkable affinity and specificity of this transporter for GSH; in fact, K-m value is very low (90 +/- 20 mu M) and only compound s strictly related to GSH structure, such as GSH S-conjugates and GSH- ethyl ester, inhibit GSH uptake in 1407 cells. Finally, a possible hor monal control and modulation by the thiol-disulfide status of GSH tran sporter activity is suggested. (C) 1997 Elsevier Science B.V.