TRANSPORT MECHANISMS OF ENOXACIN IN RAT BRUSH-BORDER MEMBRANE OF RENAL-CORTEX - INTERACTION WITH ORGANIC CATION-TRANSPORT SYSTEM AND IONIC-DIFFUSION POTENTIAL-DEPENDENT UPTAKE

The mechanism of the renal transport of enoxacin (ENX) has been invest igated using brush-border membrane vesicles (BBMV's) isolated from the rat renal cortex. The initial rate and time-course of ENX uptake were quite dependent upon the medium pH (pH 5.5 > pH 7.5). The pH dependen ce was in accordance with the degree of cationic form. Carbonyl cyanid e p-(trifluoromethoxy)phenylhydrazone (FCCP) affected the transient up hill transport of ENX across the renal brush-border membrane in the pr esence of an outward-directed H+-gradient. The initial uptake Has satu rable, and transport kinetic parameters were given for a K-m and V-max of 0.59 mM and 1.37 nmol/(mg protein)/30 s, respectively. On the othe r hand, an outward H+-gradient (pH(in)=5.5, (out)=7.5) dependent uptak e of ENX was partially decreased by the voltage-clamped BBMVs. Further more, a valinomycin-induced K+-diffusion potential (interior negative) was found to increase the uptake of ENX at pH 5.5,, which is cationic form-rich. These results suggest that ENX uptake participates in not only the H+/organic cation antiport system for organic cation secretio n but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.