Changes in the permeation rate of organic anions through the intestinal brush-border membrane with membrane surface potential.
The effects of membrane surface potential on the uptake of anionic compounds by rat intestinal brush-border membrane vesicles were investigated. The uptake amount of all tested anionic compounds (ceftibuten, cefixime, benzylpenicillin, s-1006 and rentiapril) in the neutral medium (pH 7.5) was lower than that in the acidic medium (pH 5.5). Changes in surface potential of brush-border membrane vesicles were monitored using a fluorescence dye, 8-anilino-1-naphthalenesulfonate (ANS), and the results suggested an increase of a negative charge on the membrane surface proportional to the increase of the pH of medium. A good correlation was observed between the initial uptake rate of all tested anionic compounds and relative membrane surface potential monitored by ANS. Moreover, the uptake of cefixime by artificial liposome made from PC containing various amount of DPPS was measured. The uptake value of cefixime was decreased in proportion to an increase of DPPS content. These results suggest that the permeation of anionic compounds across intestinal brush-border membrane is dependent on surface potential originate in the surface negative charge.
Sugawara
M
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Hashimoto
A
A
Toda
T
T
Takahashi
M
M
Kobayashi
M
M
Iseki
K
K
Miyazaki
K
K
D000817:Anilino Naphthalenesulfonates; D000818:Animals; D000838:Anions / Q000378:metabolism*; D020682:Cefixime; D002439:Cefotaxime / Q000031:analogs & derivatives / Q000378:metabolism; D000077722:Ceftibuten; D002511:Cephalosporins / Q000378:metabolism; D004058:Diffusion; D005456:Fluorescent Dyes; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism*; D008564:Membrane Potentials; D008871:Microvilli / Q000378:metabolism*; D010400:Penicillin G / Q000378:metabolism; D010539:Permeability; D051381:Rats
D000817:Anilino Naphthalenesulfonates; D000838:Anions; D002511:Cephalosporins; D005456:Fluorescent Dyes; C027132:1-anilino-8-naphthalenesulfonate; D020682:Cefixime; D000077722:Ceftibuten; D002439:Cefotaxime; D010400:Penicillin G