Transport Mechanisms of Enoxacin in Rat Brush-Border Membrane of Renal Cortex: Interaction with Organic Cation Transport System and Ionic Diffusion Potential Dependent Uptake

摘要

The mechanism of the renal transport of enoxacin (ENX) has been investigated using brush-border membrane vesicles (BBMVs) 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 dependence was in accordance with the degree of cationic form. Carbonyl cyanide/j-^rifluoromethoxyjphenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H+-gradicnt. The initial uptake was saturable, and transport kinetic parameters were given for a Km and Fmax of 0.59 mM and 1.37nmol/(mg protein)/30 s, respectively. On the other hand, an outward H+-gradient (pHin = 5.5, m,, = 7.5) dependent uptake of ENX was partially decreased by the voltage-clamped BBMVs. Furthermore, 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 secretion but also the ionic diffusion potential (interior negative) dependent permeation through the membrane.