Effect of cationic drugs on Na⁺-dependent carrier mediated transport and its evaluation

Abstract

We investigated the effect of cationic drugs on carrier mediated transport using in vitro and in situ techniques. The initial uptake of glucose, alanine and glutamic acid by rat intestinal brush border membrane vesicles(BBMV) was distinctly inhibited by imipramine in the presence of Na⁺ gradient, but not inhibited in the absence of Na⁺ gradient. This result indicates that imipramine inhibited carrier mediated transport. Imipramine exhibited competitive inhibition with respect to Na⁺ concentration, while exhibited non-competitive inhibition with respect to glutamic acid concentration. This finding suggests that imipramine affected carrier mediated transport by competitive inhibition to Na⁺ binding site of the carrier. On the other hand, in situ single pass perfusion method showed that absorption of alanine was also inhibited by imipramine and other cationic drugs in the presence of Na⁺, but not inhibited in the absence of Na⁺. This result is agreement with that of BBMV study. The inhibition of carrier mediated alanine transport by cationic drugs in BBMV corresponded to that in situ. There was a relatively good correlationship between the BBMV study and in situ perfusion study in the inhibitory effects.