H+ coupled uphill transport of aminocephalosporins via the dipeptide transport system in rabbit intestinal brush-border membranes.
The transport characteristics of aminocephalosporin antibiotics, possessing an alpha-amino group and a carboxyl group, in brush-border membranes isolated from rabbit small intestine have been studied by a rapid filtration technique. The uptake of cephradine by brush-border membrane vesicles was stimulated by the countertransport effect of dipeptides, which indicates the existence of a common carrier transport system. An inward H+ gradient ([pH]i = 7.5 to 8.4, [pH]o = 6.0) stimulated cephradine uptake against a concentration gradient (overshoot phenomenon), and this stimulation was reduced when the H+ gradient was subjected to rapid dissipation by the presence of carbonyl cyanide p-trifluoromethoxyphenylhydrazone, a protonophore. A valinomycin-induced K+ diffusion potential (interior-negative) stimulated H+ gradient-dependent cephradine uptake without altering the equilibrium value. The uptake of other aminocephalosporins (cefadroxil, cefaclor, cephalexin) was also stimulated in the presence of an inward H+ gradient, while the uptake of cephalosporins without the alpha-amino group (cefazolin, cefotiam) was not changed in the presence or absence of the H+ gradient. These results suggest that the transport of aminocephalosporins can be driven actively by an inward H+ gradient via the dipeptide transport system in the intestinal brush-border membranes, and that the process results in the transfer of a positive charge.
D000818:Animals; D001693:Biological Transport, Active; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002511:Cephalosporins / Q000378:metabolism*; D002515:Cephradine / Q000378:metabolism; D004151:Dipeptides / Q000378:metabolism*; D006863:Hydrogen-Ion Concentration; D007422:Intestines / Q000648:ultrastructure*; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism; D011522:Protons; D011817:Rabbits
D002511:Cephalosporins; D004151:Dipeptides; D011522:Protons; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D002515:Cephradine