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 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 1.37nmol/(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 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.
Hirano
T
T
Faculty of Pharmaceutical Sciences, Health Sciences University of Hokkaido, Japan.
Iseki
K
K
Sugawara
M
M
Miyazaki
S
S
Takada
M
M
Miyazaki
K
K
D000818:Animals; D002412:Cations; D004058:Diffusion; D015365:Enoxacin / Q000493:pharmacokinetics*; D006863:Hydrogen-Ion Concentration; D015640:Ion Channel Gating; D007473:Ion Channels / Q000378:metabolism / Q000502:physiology; D017136:Ion Transport; D007672:Kidney Cortex / Q000378:metabolism*; D008297:Male; D008871:Microvilli / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D002412:Cations; D007473:Ion Channels; D015365:Enoxacin