Inhibitory effects of basic drugs on the sodium-dependent transport of L-alanine via system B0 in the small intestine.
To elucidate the mechanism of the interaction of basic drugs with Na(+)-dependent L-alanine absorption from the small intestine, we investigated the effect of imipramine on the transport of L-alanine via system B(0), which is thought to be one of the main Na(+)-dependent systems for intestinal absorption of short-chain neutral amino acids, including L-alanine. The uptake of L-alanine by cells that express hATB(0) (human amino acid transporter B(0)) was inhibited in the presence of imipramine. The Eadie-Hofstee plot showed that the inhibition was not competitive with the substrate (L-alanine) but competitive with Na(+). When rat intestinal brush border membrane vesicles were used, several basic drugs had inhibitory effects. Inhibition was also observed in intestinal absorption evaluated by an in situ single-pass perfusion technique. However, the potencies of inhibition were different. The potency of inhibition was dependent on the lipophilicity of the drugs.
Sugawara
Mitsuru
M
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo, Japan.
Kato
Masaya
M
Kitakubo
Mayumi
M
Takekuma
Yoh
Y
Ganapathy
Vadivel
V
Miyazaki
Katsumi
K