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 org anic cation on the Na+-dependent transport of L-glutamic acid across i ntestinal brush-border membrane was investigated. The uptake of L-glut amic acid by intestinal brush-border membrane vesicles was dependent o n the concentration of Na+. Fitting of the uptake; data in the presenc e 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 imipr amine inhibits the transport of L-glutamic acid by interacting competi tively 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+ mole cule was also suggestive of interaction with the Na+-binding sites on the carrier. These results indicate that the mechanism of the inhibito ry effect of imipramine on the Na+-dependent carrier systems is common for all systems regardless of the stoichiometry or substrates. (C) 19 98 Elsevier Science B.V.