SECRETION OF CYSTEINE AND GLUTATHIONE FROM MUCOSA TO LUMEN IN RAT SMALL-INTESTINE

Using a vascularly perfused rat intestinal preparation, we found that large quantities (i.e., 100-200 mu M) of acid-soluble thiols accumulated in the jejunal lumen in 10-30 min and that the accumulation was largely unaffected by dietary food restriction for 24 or 48 h. Depending on the length of perfusion, cysteine comprised 20-40% of total luminal thiols, whereas glutathione (GSH) made up only 0-3%. To determine whether luminal cysteine accumulation resulted from mucosal secretion of GSH and subsequent degradation by brush-border gamma-glutamyltransferase (gamma-GT) and dipeptidases, acivicin or serine-borate was used to inhibit gamma-GT. Both agents inhibited gamma-GT activity by > 95%, reduced luminal cysteine by similar to 40-50%, and caused a modest elevation of luminal GSH to similar to 10-13 mu M, indicating that GSH secretion does occur but cannot account for all of the luminal cysteine accumulation. Luminal thiol trapping experiments with Ellman's reagent supported this conclusion. Given that cysteine made up 15-20% of the mucosal thiol pool in jejunum, secretion of cysteine from mucosa to lumen likely accounted for the majority of luminal cysteine. Given the mucolytic nature of thiols and the role of cysteine in iron absorption, intestinal thiol secretion may be important in intestinal function.