Related Experiment Video

Updated: Aug 23, 2026

An Assay for Quantifying Protein-RNA Binding in Bacteria
07:02

An Assay for Quantifying Protein-RNA Binding in Bacteria

Published on: June 12, 2019

Mrp2 is involved in benzylpenicillin-induced choleresis

Kousei Ito1, Tomokazu Koresawa, Koichi Nakano

  • 1Laboratory of Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 263-8675, Japan.

American Journal of Physiology. Gastrointestinal and Liver Physiology
|June 15, 2004
PubMed

Insights

Benzylpenicillin

Area of Science:

  • Pharmacology and Toxicology
  • Drug Metabolism and Transport
  • Hepatobiliary Physiology

Background:

  • Benzylpenicillin (PCG) is a widely used beta-lactam antibiotic.
  • The multidrug resistance-associated protein 2 (Mrp2) is a key transporter in biliary excretion.
  • The role of Mrp2 in PCG's biliary excretion and its choleretic effects is not fully understood.

Purpose of the Study:

  • To investigate the role of Mrp2 in the biliary excretion of benzylpenicillin.
  • To determine if Mrp2 mediates the choleretic effect of benzylpenicillin.
  • To elucidate the mechanisms underlying PCG-induced bile flow changes.

Main Methods:

  • Intravenous administration of [(3)H]benzylpenicillin to Sprague-Dawley (SD) rats and Mrp2-deficient Eisai hyperbilirubinemic rats (EHBR).
  • Measurement of biliary excretion of PCG and bile flow.
  • In vitro studies using Sf9 membrane vesicles and Madin-Darby canine kidney II cells expressing human MRP2 to assess PCG and glutathione (GSH) transport.

Main Results:

  • Significantly lower biliary excretion of PCG in EHBR (4.3%) compared to SD rats (31.7%).
  • PCG administration caused a 2-fold increase in bile flow and bilirubin excretion in SD rats, but not in EHBR.
  • PCG enhanced GSH efflux mediated by human MRP2 in a concentration-dependent manner, suggesting Mrp2 involvement.

Conclusions:

  • The biliary excretion of benzylpenicillin and its choleretic effect are dependent on the Mrp2 transporter.
  • PCG stimulates bile flow by enhancing biliary glutathione (GSH) efflux via Mrp2.
  • Concentrative biliary excretion of PCG itself, mediated by Mrp2, also contributes to its pharmacological action.

More Related Videos

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa13:40

In vitro Investigation of the MexAB Efflux Pump From Pseudomonas aeruginosa

Published on: February 17, 2014

Laboratory Techniques Used to Maintain and Differentiate Biotypes of Vibrio cholerae Clinical and Environmental Isolates07:58

Laboratory Techniques Used to Maintain and Differentiate Biotypes of Vibrio cholerae Clinical and Environmental Isolates

Published on: May 30, 2017

Related Concept Videos

Mechanism of Antibiotic Resistance in MRSA01:25

Mechanism of Antibiotic Resistance in MRSA

Antibiotic resistance in bacteria arises when microorganisms evolve the ability to withstand drugs designed to kill them or inhibit their growth, rendering once-effective treatments useless. This phenomenon, driven by genetic change and selection under antibiotic exposure, poses a profound threat to modern medicine. Mechanisms include drug-inactivating enzymes (e.g., β-lactamases), efflux pumps that eject antibiotics, mutations altering antibiotic targets, decreased drug uptake, and acquisition...
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Clinical Significance of Antibiotic Resistance01:25

Clinical Significance of Antibiotic Resistance

Methicillin-resistant Staphylococcus aureus (MRSA) presents a critical public health threat, arising from its capacity to resist β-lactam antibiotics due to acquisition of the mecA gene within the staphylococcal cassette chromosome mec (SCCmec). This gene encodes penicillin-binding protein 2a (PBP2a), which impairs binding efficacy of methicillin and other β-lactams. MRSA has evolved into distinct clonal lineages impacting humans and animals alike, reinforcing its significance within the One...
Production of Antibiotics01:27

Production of Antibiotics

Penicillin, one of the earliest and most widely used antibiotics, is produced industrially by the filamentous fungus Penicillium chrysogenum. Large stirred-tank bioreactors ranging from tens to hundreds of thousands of liters maintain tightly controlled temperature, pH, and dissolved oxygen conditions to support fungal metabolism and maximize antibiotic yield. Penicillin is a secondary metabolite, synthesized primarily during the stationary growth phase, which requires a carefully managed...
Repressible Operon: trp Operon01:21

Repressible Operon: trp Operon

The trp operon in Escherichia coli exemplifies a repressible operon. It regulates the synthesis of tryptophan through repressor-mediated transcriptional control and attenuation. This dual regulatory mechanism ensures tryptophan biosynthesis occurs only when needed, conserving cellular resources.Structure of the trp OperonThe trp operon consists of five structural genes (trpE, trpD, trpC, trpB, and trpA) that encode enzymes for tryptophan biosynthesis. These genes are transcribed as a single...
Coordination of Gene Expression Processes in Bacteria01:29

Coordination of Gene Expression Processes in Bacteria

The DNA replication, transcription, and translation processes are intricately coupled in bacteria, allowing efficient gene expression and rapid protein synthesis. While this physical and functional coordination is advantageous, it introduces challenges that bacteria overcome through specific regulatory mechanisms.Coupling of Replication, Transcription, and TranslationThe coupling of replication, transcription, and translation is a hallmark of bacterial gene expression. As the replisome unwinds...