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Updated: Sep 30, 2026

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms
08:46

Implementation of In Vitro Drug Resistance Assays: Maximizing the Potential for Uncovering Clinically Relevant Resistance Mechanisms

Published on: December 9, 2015

Tissue distribution and chemical induction of multiple drug resistance genes in rats

James M Brady1, Nathan J Cherrington, Dylan P Hartley

  • 1Deptartment of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas 66160, USA.

Drug Metabolism and Disposition: the Biological Fate of Chemicals
|June 18, 2002
PubMed

Insights

Rat mdr1 genes, crucial for xenobiotic transport, are primarily expressed in the gastrointestinal tract. Microsomal enzyme inducers do not significantly alter mdr1 gene expression in rats.

Area of Science:

  • Pharmacology
  • Molecular Biology
  • Toxicology

Background:

  • Multiple drug resistance (mdr) genes encode P-glycoprotein, facilitating xenobiotic efflux and conferring cellular resistance to drugs.
  • MDR proteins play a protective role in organs by limiting xenobiotic absorption.
  • Rats possess two mdr1 genes, mdr1a and mdr1b, involved in xenobiotic transport.

Purpose of the Study:

  • To investigate the tissue distribution of rat mdr1a and mdr1b mRNA.
  • To determine if microsomal enzyme inducers coordinately regulate mdr1a and/or mdr1b gene expression.

Main Methods:

  • Quantification of mdr1a and mdr1b mRNA levels using branched-DNA signal amplification technology.
  • Assessment of mdr1a and mdr1b mRNA induction in liver, kidney, and ileum following treatment with various chemical inducers.

Main Results:

  • Highest expression of mdr1a mRNA was found in the gastrointestinal tract (duodenum, jejunum, ileum, large intestine).
  • mdr1b mRNA distribution was similar to mdr1a, with peak expression in the gastrointestinal tract.
  • Hepatic, renal, and intestinal mdr1a and mdr1b mRNA levels were not significantly altered by any tested classes of microsomal enzyme inducers.

Conclusions:

  • Rat mdr1 genes are predominantly expressed in the gastrointestinal tract, likely functioning to reduce xenobiotic absorption.
  • Microsomal enzyme inducers do not readily increase rat mdr1 gene expression through coordinate regulation with drug-metabolizing enzymes.

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