The Transport Mechanism of an Organic Cation, Disopyramide, by Brush-border Membranes. Comparison Between Renal Cortex and Small Intestine of the Rat

Author:

Takahashi Yasushi1,Itoh Tatsuya2,Kobayashi Michiya3,Sugawara Mitsuru3,Saitoh Hiroshi3,Iseki Ken3,Miyazaki Katsumi3,Miyazaki Shozo2,Takada Masahiko2,Kawashima Yoshiaki4

Affiliation:

1. Department of Pharmacy, Sapporo City General Hospital, Kita-1-jo, Nishi-9-chome, Chuo-ku, Sapporo 060

2. Faculty of Pharmaceutical Sciences, Higashi-Nippon-Gakuen Univerity, Ishikari-Tobetsu, Hokkaido 061–02

3. Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Kita-14-jo, Nishi-5-chome, Kita-ku, Sapporo 060

4. Gifu College of Pharmacy, Mitahora, Gifu 502, Japan

Abstract

Abstract The characteristics of disopyramide uptake in brush-border membrane vesicles isolated from rat renal cortex and small intestine were investigated. Transport of disopyramide into an osmotically reactive intravesicular space was observed with notable binding to the membrane surface. An outwardly directed H+ gradient stimulated disopyramide uptake, resulting in a transient uphill transport in both brush-border membranes. As for the renal brush-border membrane, the H+ gradient itself appeared to be the driving force for this stimulation of uptake. These findings suggest that disopyramide-H+ antiport is the mechanism of disopyramide action in renal cell membrane. The initial uptake was saturable (Km and Vmax of 680 μm and 1·25 nmol (mg protein)−1/30 s, respectively). The stimulation of disopyramide uptake by an outward H+ gradient in rat intestinal brush-border membrane was due to an interior negative H+-diffusion potential. A K+-diffusion potential (interior negative) enhanced disopyramide uptake. These results suggest that there are different mechanisms of disopyramide uptake for renal and intestinal brush-border membrane vesicles.

Publisher

Oxford University Press (OUP)

Subject

Pharmaceutical Science,Pharmacology

Reference28 articles.

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2. Properties of brush border vesicles isolated from rat kidney cortex by calcium precipitation;Evers;Membr. Biochem.,1978

3. Cimetidine transport in isolated luminal membrane vesicles from rabbit kidney;Gisclon;Am. J. Physiol.,1987

4. Inhibitory effect of diethyl pyrocarbonate on the H+/organic cation antiport system in rat renal brush-border membranes;Hori;J. Biol. Chem.,1989

5. H+-Gradient-dependent active transport of tetraethylammonium cation in apical-membrane vesicles isolated from kidney epithelial cell line LLC-PK1;Inui;Biochem. J.,1985

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