EFFECTS OF BILE-SALTS ON BRUSH-BORDER AND CYTOSOLIC PROTEOLYTIC ACTIVITIES OF INTESTINAL ENTEROCYTES

The effects of bile salts, i.e., sodium deoxycholate, sodium glycocholate, sodium glycodeoxycholate, sodium taurocholate, and sodium taurodeoxycholate, on the activities of individual rat intestinal brush-border membrane peptidases and cytosolic insulin-degrading activities were examined. At 2 mM, bile salts had no effects on aminopeptidases P and W, but did inhibit other brush-border peptidases though no single bile salt was able to inhibit every peptidase. Even at concentrations higher than the CMC, inhibition of brush-border insulin degradation is incomplete while that of cytosolic insulin degradation is complete at low concentrations. The results suggest that bile salts, inhibiting brush-border membrane and cytosolic proteolytic hydrolysis, may be useful for reducing intestinal degradation of peptide drugs; and that bile salts have stronger inhibitory effects on soluble than on membrane-bound insulin-degrading activity.