THE INHIBITORY EFFECTS OF CEPHALOSPORIN AND DIPEPTIDE ON CEFTIBUTEN UPTAKE BY HUMAN AND RAT INTESTINAL BRUSH-BORDER MEMBRANE-VESICLES

The types of inhibitory effects caused by compound V (an analogue of c eftibuten) and alanylproline (dipeptide) on the uptake of ceftibuten b y brush-border membrane vesicles (BBMV) prepared from human and rat sm all intestine were analysed. In the presence of an inward H+-gradient, the initial uptake rate of ceftibuten by both human and rat intestina l BBMV was concentration-dependent with apparent K-m and V-max values of 0.35 mM and 2.052 nmol (mg protein)(-1) min(-1) for human BBMV, and 0.50 mM and 3.056 nmol (mg protein)(-1) min(-1) for rat BBMV, respect ively. For both human and rat BBMV, kinetic analysis by Dixon and Line weaver-Burk plots demonstrated that the uptake of ceftibuten was compe titively inhibited by compound V, whereas inhibition by alanylproline was noncompetitive or partially competitive. These results suggest tha t there is a stereospecific transport system which is common to ceftib uten and compound V, and that this system is not identical to the carr ier system for the dipeptide, alanylproline.