Inhibitory Effects of Basic Drugs on the Sodium-Dependent Transport of L-Alanine via System B⁰ in the Small Intestine

Abstract

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 B⁰, 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 hATB⁰ (human amino acid transporter B⁰) 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.