Transport characteristics of S-1090, a new oral cephem, in rat intestinal brush-border membrane vesicles.

PURPOSE

Elucidating the transport characteristics of S-1090, a new orally active cephalosporin in rat small intestinal brush-border membranes.

METHODS

A rapid filtration technique.

RESULTS

The uptake of S-1090 was stimulated by an inwardly directed H(+)-gradient, but did not show overshooting uptake. To investigate the transport system, the inhibitory and countertransport effects of various compounds on S-1090 uptake were examined. Although the dipeptides and tripeptides composed of amino acids with aliphatic side chains did not inhibit the uptake of S-1090, those having histidine, proline or tryptophan as the N-terminal amino acid showed an inhibitory effect. Among the oral cephems tested, ceftibuten showed marked inhibition, while cefaclor and cephalexin had no inhibitory effect. Countertransport effects on S-1090 uptake were observed only when the vesicles were preloaded with histidyl peptides such as His-Gly or His-Ala, while other compounds which exhibited inhibition had no countertransport effect.

CONCLUSIONS

Based on the above results, there seems to be heterogeneity (multiplicity) in the oligopeptide transport system which may depend on the structure of the N-terminal amino acid. S-1090 may be dominantly transported via a system that recognizes peptides having histidine as the N-terminal amino acid.