Ionic-diffusion potential-dependent transport of a new quinolone, sparfloxacin, across rat intestinal brush-border membrane

The mechanism of uptake of sparfloxacin, a new quinolone, by intestinal bru sh-border membrane vesicles was investigated to clarify whether there is a common transport process for new quinolones mediated by the diffusion poten tial across the intestinal membrane bilayer. Sparfloxacin was taken up pH-dependently by rat intestinal brush-border mem brane vesicles, behaviour analogous to that of organic cations including en oxacin and ciprofloxacin. Transient overshooting uptake of this quinolone w as observed in the presence of an outward H+ gradient. Momentary dissipatio n of the H+ gradient by addition of carbonyl cyanide p-(trifluoromethoxy)ph enylhydrazone did not affect the uptake of sparfloxacin, and a marked but i ncomplete reduction in the H+-sensitive overshooting uptake of sparfloxacin was apparent in the voltage-clamped brush-border membrane vesicles. Furthe rmore, a valinomycin-induced K+-diffusion potential (interior negative) and an inward Cl(-)diffusion potential stimulated the initial uptake of sparfl oxacin at pH 5.5. Sparfloxacin uptake was inhibited by tetracaine and imipr amine. The inhibitory effect of these cations correlated well with changes in membrane surface charges induced by the presence of tetracaine or imipra mine. These results indicate that sparfloxacin transport across the brush-border membrane depends upon the inside-negative ionic diffusion potential, that t he H+ - or K+-diffusion-potential-dependent uptake of sparfloxacin by intes tinal brush-border membrane vesicles is affected by the membrane surface po tential and that inhibition of sparfloxacin uptake originates from changes in the membrane surface potential caused by the organic cations.