A COMPARISON OF THE AFFINITIES OF DIPEPTIDES AND ANTIBIOTICS FOR THE DIPEPTIDE TRIPEPTIDE TRANSPORTER IN CACO-2 CELLS/

The intestinal peptide transporter(s) is involved in the absorption of natural di-/tripeptides and peptidomimetic drugs. Several key aspects of peptide transport such as number of peptide transporters and struc tural requirements for transport via this carrier(s) are not fully und erstood. In addition, recent studies showed that interaction with the di-/tripeptide transporter(s) does not necessarily lead to transcellul ar transport. The variety of structures which appear to interact with the transporter could be explained by the presence of several transpor ters or by multiple binding sites in a single transporter. The objecti ve of this study was to determine whether there is a clear difference between dipeptides and amino-p-lactam antibiotics which may suggest th e involvement of different transporters/binding sites. Experiments wer e carried out in Caco-2 cell monolayers grown on microporous membranes using cephalexin as the model compound. Inhibition constants (K-1) we re calculated from Dixon plots assuming competitive inhibition. The st rong correlation between K-i and IC50 (independently determined) indic ates that the assumption of competitive inhibition was probably correc t. Results show: (a) that dipeptides have greater affinity for the cep halexin transporter(s) than antibiotics; (b) among dipeptides, neutral dipeptides seem to have higher affinity for the carrier; and (c) a re lationship between affinity for the transporter(s) and transepithelial transport could not be found.