Sugawara M, Kato M, Kobayashi M, Iseki K, Miyazaki K
Department of Pharmacy, Hokkaido University Hospital, School of Medicine, Hokkaido University, Sapporo 060, Japan.
Biochim Biophys Acta. 1998 Mar 13;1370(2):252-8. doi: 10.1016/s0005-2736(97)00270-8.
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.
研究了亲脂性有机阳离子丙咪嗪对L-谷氨酸钠依赖性跨肠刷状缘膜转运的抑制作用机制。肠刷状缘膜囊泡对L-谷氨酸的摄取取决于Na+浓度。用Hill方程拟合不同浓度Na+存在下的摄取数据，得到的Hill系数为2.18。这一结果表明，L-谷氨酸的载体系统至少有两个Na+结合位点。通过双倒数图和Dixon型图分析发现，丙咪嗪通过与Na+结合位点竞争性相互作用抑制L-谷氨酸的转运，但不抑制L-谷氨酸结合位点。此外，丙咪嗪对仅与一个Na+分子共转运的L-丙氨酸和D-葡萄糖转运的影响也提示其与载体上的Na+结合位点相互作用。这些结果表明，丙咪嗪对Na+依赖性载体系统的抑制作用机制对所有系统都是相同的，无论其化学计量或底物如何。
