PMID: 9545575May 16, 1998Paper

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

Biochimica Et Biophysica Acta
M SugawaraK Miyazaki

Abstract

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.

References

Feb 28, 1985·Biochimica Et Biophysica Acta·B ElsenhansW F Caspary
Sep 1, 1974·The Biochemical Journal·A G Booth, A J Kenny
Nov 18, 1980·Biochimica Et Biophysica Acta·H HauserD E Bowyer
Jan 1, 1982·The Journal of Membrane Biology·B R StevensE M Wright
Jul 14, 1995·The Journal of Biological Chemistry·Y KanaiM A Hediger

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Citations

Dec 25, 2004·Drug Metabolism and Pharmacokinetics·Mitsuru SugawaraKatsumi Miyazaki
Jun 20, 2008·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Keiko Shimamoto

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