EFFECT OF MEMBRANE SURFACE POTENTIAL ON THE PERMEATION OF IONIC DRUGS THROUGH THE INTESTINAL BRUSH-BORDER MEMBRANE

Abstract

The effect of membrane surface potential on the permeation of ionic compounds through the intestinal brush-border membrane was investigated using uptake experiments by brush-border membrane vesicles (BBMV) and large unilamellar vesicles (LUV). The uptake of anionic compounds (ceftibuten, cefixime, benzylpenicillin etc.) was decreased with increase of membrane surface negativity. On the other hand, the uptake of a cationic compound, tryptamine, was increased with increase of surface negativity. The uptake of these ionic compounds was well correlated with membrane surface potential of BBMV and LUV monitored by ANS. These results suggest that the permeation of ionic compounds through the intestinal brush-border membrane is dependent on the membrane surface potential. The mechanism of inhibitory effect on the uptake among these Ionic compounds was also examined from the viewpoint of changes in the membrane surface potential. The inhibitory effect of tetracaine and imipramine on the uptake of tryptamine was well correlated with changes in the membrane surface potential induced by these organic cations. Similar relation was observed in the inhibitory effect of flufenamic acid on the uptake of cefixime. These results suggest that changes in the membrane surface potential contribute to the inhibitory effect on the uptake of these Ionic compounds.