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

• Published in: Biological & pharmaceutical bulletin 1995/02/15, Vol.18(2), pp.342-346
• Main Authors: HIRANO, Takeshi, ISEKI, Ken, SUGAWARA, Mitsuru, MIYAZAKI, Shozo, TAKADA, Masahiko, MIYAZAKI, Katsumi
• Format: Article
• Language: English
• Subjects: Animals; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Biological and medical sciences; brush-border membrane (BBM); Cations; Diffusion; enoxacin (ENX); Enoxacin - pharmacokinetics; H+/organic cation antiport; Hydrogen-Ion Concentration; Ion Channel Gating; Ion Channels - metabolism; Ion Channels - physiology; Ion Transport; Kidney Cortex - metabolism; Male; Medical sciences; membrane potential; membrane transport; Microvilli - metabolism; Pharmacology. Drug treatments; Rats; Rats, Wistar; renal proximal tubule
• ISSN: 0918-6158; 1347-5215
• DOI: 10.1248/bpb.18.342

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 p-(trifluoromethoxy) phenylhydrazone (FCCP) affected the transient uphill transport of ENX across the renal brush-border membrane in the presence of an outward-directed H+-gradient. The initial uptake was saturable, and transport kinetic parameters were given for a Km and Vmax of 0.59mM and 1.37 nmol/ (mg protein)/30s, respectively. On the other hand, an outward H+-gradient (pHin=5.5, out=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 pH5.5, which is cationic from-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.