Mechanism of the inhibitory effect of imipramine on the Na+-dependent transport of L-glutamic acid in rat intestinal brush-border membrane.

The mechanism of the inhibitory effect of imipramine, a lipophilic organic cation on the Na+-dependent transport of L-glutamic acid across intestinal brush-border membrane was investigated. The uptake of L-glutamic acid by intestinal brush-border membrane vesicles was dependent on the concentration of Na+. Fitting of the uptake data in the presence of various concentrations of Na+ using Hill equation yielded a Hill coefficient of 2.18. This result suggest that the carrier system of L-glutamic acid has at least two sites for Na+-binding. By the analysis of double reciprocal plot and Dixon-type plot, it was found that imipramine inhibits the transport of L-glutamic acid by interacting competitively with the binding sites of Na+, but not inhibit L-glutamic acid binding site. Moreover, the effect of imipramine on the transport of L-alanine and D-glucose which are co-transported with only one Na+ molecule was also suggestive of interaction with the Na+-binding sites on the carrier. These results indicate that the mechanism of the inhibitory effect of imipramine on the Na+-dependent carrier systems is common for all systems regardless of the stoichiometry or substrates. Copyright 1998 Elsevier Science B.V.