H+ GRADIENT-DEPENDENT AND CARRIER-MEDIATED TRANSPORT OF CEFIXIME, A NEW CEPHALOSPORIN ANTIBIOTIC, ACROSS BRUSH-BORDER MEMBRANE-VESICLES FROM RAT SMALL-INTESTINE

  • 1 May 1987
    • journal article
    • research article
    • Vol. 241  (2) , 594-601
Abstract
The characteristics of the transport of cefixime, a new p.o. cephalosporin, antibiotic, were studied by using brush-border membrane vesicles from the rat small intestine. The initial rate of uptake of cefixime was not affected by the presence of an inward gradient of either Na+ or other monovalent cations. With and intravesicular pHi of 7.5, optimal cefixime uptake occurred at an extravesicular pHo of 5.0, with about 6-fold accleration compared with that in the absence of an inward proton gradient (pHi = pHo = 7.5). A protonophore, carbonyl-cyanide-4-trifluoromethoxy,-phenylhydrazone, abolished the stimulating effect of low pHo. In the presence of a sufficient inward proton gradient (pHi = 7.5, pHo = 5.0), cefixime uptake showed an overshoot phenomenon and apparent saturation kinetics expressed by the Michaelis-Menten equation with the maximum rate of 2.67 .+-. 0.06 nmol/30 sec/mg of protein and a Michaelis constant of 0.83 .+-. 0.04 mM. Cefixime uptake was inhibited competitively by glycyl-L-proline and stimulated by the countertransport effect of this dipeptide. The other peptides also inhibited cefixime uptake significantly. A valinomycin-induced inside-negative K+-diffusion potential had a dramatic reducing effect on the uptake of dianionic cefixime. All the data obtained in this study demonstrate that cefixime transports across the brush-border membrane vesicles is carrier-mediated, independent of Na+ and dependent on a H+ gradient via the peptide transport systems.

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