头孢羟氨苄
头孢克肟
运输机
细胞内pH值
碳酸钙-2
化学
生物化学
细胞内
生物物理学
爪蟾
生物
药理学
分子生物学
细胞
头孢菌素
抗生素
基因
作者
U. Wenzel,I Gebert,Horst Weintraut,W. Weber,Wolfgang Clauss,Hannelore Daniel
出处
期刊:PubMed
日期:1996-05-01
卷期号:277 (2): 831-9
被引量:33
摘要
To investigate whether multiple peptide transporters mediate absorption of beta-lactams carrying different charges at physiological pH, we used the human intestinal cell line Caco-2 and Xenopus laevis oocytes expressing the cloned rabbit intestinal peptide transporter PepT1. Characteristics of transport of the anionic cefixime and the zwitterionic cefadroxil were assessed by 1) flux studies using radiolabeled compounds, by 2) measuring changes in pHin in cells and oocytes as a consequence of substrate-mediated proton influx and 3) by applying the two-electrode voltage clamp technique to assess the electrophysiological phenomena associated with beta-lactam transport in oocytes expressing PepT1. Both beta-lactams were rapidly taken up into Caco-2 cells and oocytes expressing PepT1 by a pH-dependent and saturable transport pathway. Mutual inhibition suggested that acidic and zwitterionic compounds may share a common transporter. Cefixime and cefadroxil caused a significant decline in intracellular pH as a consequence of proton coupled substrate influx. Uptake of cefixime and cefadroxil via PepT1 expressed in oocytes was electrogenic indicating that transport of both beta-lactams is associated with movement of net positive charge. The more acidic pH required for rheogenic cefixime uptake in both cell systems, when compared to cefadroxil uptake in both cell systems, when compared to cefadroxil uptake, and the concomitant faster intracellular acidification indicates that cefixime most likely is taken up only in its nonionized form with an additional proton being cotransported. This is supported by the observation that cefixime uptake at different pH correlated significantly with the percentage of the nonionized species being present. From our studies we conclude that a single peptide transport system can mediate electrogenic uptake of the neutral form of beta-lactam antibiotics into intestinal epithelial cells.
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