THE INHIBITION OF INTESTINAL DIPEPTIDYLAMINOPEPTIDASE-IV PROMOTES THEABSORPTION OF ENTEROSTATIN AND DES-ARGININE-ENTEROSTATIN ACROSS RAT JEJUNUM IN-VITRO

Transport of enterostatin (VPDPR) across rat jejunum was investigated using Grass-Sweetana diffusion chambers. The rate of absorption of ent erostatin and its metabolites were studied in absence and in presence of diisopropylfluorophosphate (DFP), a serine protease inhibitor. An e xtensive hydrolysis of enterostatin was observed during incubation wit h brush border membranes and when exposed to the mucosal side of the j ejunal epithelium. No accumulation of enterostatin occured in serosal tissue. Addition of DFP delayed enterostatin disappearance and abolish ed des-arg-enterostatin degradation. Under these conditions, a low amo unt of enterostatin was able to cross the epithelium intact. Moreover, a substantial amount of des-arg-enterostatin is absorbed across the j ejunal epithelium, probably through passive diffusion. Thus, a decreas ed metabolic activity increased the absorption of a tetrapeptide (VPDP ). Dipeptidylaminopeptidase IV, remains a limiting step in transfer of intact enterostatin and its metabolite des-arg-enterostatin across in testinal wall.