The stimulative effect of diffusion potential on enoxacin uptake across rat intestinal brush-border membranes.
Evidence of a membrane potential dependence for enoxacin uptake by rat intestinal brush-border membrane vesicles has been found. The transient overshooting uptake of enoxacin disappeared in the voltage-clamped brush-border membrane vesicles in the presence of an outward H(+)-gradient. Momentary dissipation of the H(+)-gradient itself by carbonyl cyanide p-(trifluoromethoxy)phenylhydrazone (FCCP) did not affect the uptake of enoxacin. In contrast, enoxacin uptake was depressed by an interior positive K(+)-diffusion potential induced by valinomycin. Furthermore, not only the outward H(+)-gradient but also an inward Cl(-)-gradient caused a stimulating effect on enoxacin uptake, and the stimulation by the Cl(-)-gradient was dissipated by using voltage-clamped membrane vesicles. These results indicate that enoxacin transportation across the brush-border membrane is dependent on the ionic diffusion potential. On the other hand, neither Gly-Gly nor guanidine had any effect on enoxacin uptake by the membrane vesicles in the presence of an inward (for Gly-Gly) or outward (for guanidine) H(+)-gradient as a driving force for each transport system. Therefore, it seems that enoxacin transport through the intestinal epithelia does not participate in the carrier-mediated transport systems for Gly-Gly and guanidine.
Hirano
T
T
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Iseki
K
K
Miyazaki
S
S
Takada
M
M
Kobayashi
M
M
Sugawara
M
M
Miyazaki
K
K
D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism; D002851:Chromatography, High Pressure Liquid; D004151:Dipeptides / Q000494:pharmacology; D015365:Enoxacin / Q000378:metabolism* / Q000493:pharmacokinetics; D005998:Glycine / Q000378:metabolism / Q000494:pharmacology; D019791:Guanidine; D006146:Guanidines / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007476:Ionophores / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D011188:Potassium / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D014634:Valinomycin / Q000494:pharmacology
D002712:Chlorides; D004151:Dipeptides; D006146:Guanidines; D007476:Ionophores; D014634:Valinomycin; D015365:Enoxacin; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; D019791:Guanidine; D011188:Potassium; D005998:Glycine