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 com pounds by rat intestinal brush-border membrane vesicles were investiga ted. The uptake amount of all tested anionic compounds (ceftibuten, ce fixime, benzylpenicillin, s-1006 and rentiapril) in the neutral medium (pH 7.5) was lower than that in the acidic medium (pH 5.5). Changes i n surface potential of brush-border membrane vesicles were monitored u sing a fluorescence dye, 8-anilino-1-naphthalenesulfonate (ANS), and t he results suggested an increase of a negative charge on the membrane surface proportional to the increase of the pH of medium. A good corre lation was observed between the initial uptake rate of all tested anio nic 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 c efixime was decreased in proportion to an increase of DPPS content. Th ese results suggest that the permeation of anionic compounds across in testinal brush-border membrane is dependent on surface potential origi nate in the surface negative charge.