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Updated: May 29, 2026

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein
10:43

Expression, Detergent Solubilization, and Purification of a Membrane Transporter, the MexB Multidrug Resistance Protein

Published on: December 3, 2010

Molecular-weight-dependent, anionic-substrate-preferential transport of β-lactam antibiotics via multidrug

Shin-Ichi Akanuma1, Yasuo Uchida, Sumio Ohtsuki

  • 1Division of Membrane Transport and Drug Targeting, Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai, Japan.

Drug Metabolism and Pharmacokinetics
|September 8, 2011
PubMed

Insights

Multidrug resistance-associated protein 4 (MRP4) transports beta-lactam antibiotics, influencing their brain distribution. This study quantifies transport activity, revealing cephalosporins are most affected, aiding understanding of adverse drug effects.

Area of Science:

  • Pharmacology
  • Biochemistry
  • Drug Metabolism

Background:

  • Beta-lactam antibiotics can cause cerebral and peripheral adverse effects.
  • Multidrug resistance-associated protein 4 (MRP4) is implicated in transporting beta-lactam antibiotics and limiting their brain entry via the blood-brain barrier.

Purpose of the Study:

  • To elucidate the structure-activity relationship of MRP4-mediated transport for various beta-lactam antibiotics.
  • To quantify the transport activity of MRP4 for different classes of beta-lactam antibiotics.

Main Methods:

  • Utilized MRP4-expressing Sf9 membrane vesicles to assess transport activity.
  • Quantified MRP4 protein expression using liquid chromatography-tandem mass spectrometry.
  • Evaluated transport activity as MRP4-mediated transport per MRP4 protein (nL/min·fmol).

Main Results:

  • Cefotiam exhibited the highest MRP4-mediated transport activity (8.90 nL/min·fmol).
  • Cephalosporins showed greater MRP4 transport than penams, beta-lactamase inhibitors, penems, or monobactams.
  • Anionic cephalosporins and higher-molecular-weight anionic beta-lactams were transported more efficiently by MRP4 than their zwitterionic or lower-molecular-weight counterparts.

Conclusions:

  • Quantitative data on MRP4 transport of beta-lactam antibiotics provide insights into structure-activity relationships.
  • Findings aid in understanding MRP4-related adverse effects of beta-lactam antibiotics and their derivatives.
  • Differential transport kinetics highlight the influence of chemical properties on MRP4 interaction.

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