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Updated: Aug 16, 2026
An Intestine/Liver Microphysiological System for Drug Pharmacokinetic and Toxicological Assessment
Published on: December 3, 2020
Expression of multiple drug resistance conferring proteins in normal Chinese and Caucasian small and large intestinal
Qing Wang1, Rajinder K Bhardwaj, Dea Herrera-Ruiz
1Department of Pharmaceutics, Ernest Mario School of Pharmacy, Rutgers, The State University of New Jersey, 160 Frelinghuysen Road, Piscataway, New Jersey 08854-8022, USA.
Abstract:
Multidrug resistance conferring proteins (MDRCP) are ATP-binding cassette (ABC) transporters known to significantly influence the absorption, distribution, metabolism, and elimination (ADME) and toxic behavior of many therapeutic agents. Research in the pharmacogenomics area has suggested that mutations and variable expression patterns of these MDCRPs may exist in tissue samples from different ethnic groups. The goal of this study was to examine the expression of P-glycoprotein (PGP), sister of PGP (S-PGP), multidrug resistance protein 3 (Mdr3), multidrug resistance like proteins 1-5 (MRP 1-5), and lung resistance associated protein (LRP) in tissue slides and protein lysates derived from normal adult small or large intestines of Caucasian or Chinese origin. Our results demonstrated ubiquitous expression of PGP, MRP 1, MRP 4, and LRP in the small and large intestinal epitheliums originating from both Caucasian and Chinese origin. S-PGP, Mdr3, MRP 2, and MRP 3 exhibited variable expression in the tissue slides and protein lysates derived from the Chinese and Caucasian small and large intestines. MRP 5 was not observed in any of the samples studied. The results suggest that MDCRPs may have distinct expression profiles in the small and large intestines that potentially vary with genetic background. These studies provide a foundation for further investigations to verify these findings across a wider number of patients of different ethnic backgrounds.
Insights
Multidrug resistance conferring proteins (MDRCPs) show varied expression in the human intestine based on ethnicity. Understanding these differences in P-glycoprotein and other transporters is key for drug development.
Area of Science:
- Pharmacogenomics
- Drug Metabolism and Transport
Background:
- Multidrug resistance conferring proteins (MDRCPs), a class of ATP-binding cassette (ABC) transporters, significantly impact drug ADME and toxicity.
- Genetic variations and ethnic differences in MDRCP expression are suggested by pharmacogenomic research, potentially affecting drug efficacy and safety.
Purpose of the Study:
- To investigate the expression patterns of key MDRCPs, including P-glycoprotein (PGP), S-PGP, Mdr3, MRPs 1-5, and LRP.
- To compare these expression levels in normal small and large intestinal tissues from Caucasian and Chinese adults.
Main Methods:
- Analysis of tissue slides and protein lysates from normal adult small and large intestines.
- Examination of Caucasian and Chinese ethnic groups to identify potential variations in transporter expression.
Main Results:
- Ubiquitous expression of PGP, MRP 1, MRP 4, and LRP was observed in both ethnic groups' intestinal tissues.
- Variable expression of S-PGP, Mdr3, MRP 2, and MRP 3 was noted between Caucasian and Chinese intestinal samples.
- MRP 5 was not detected in any of the studied intestinal samples.
Conclusions:
- MDRCPs exhibit distinct expression profiles in the small and large intestines, which may be influenced by genetic background and ethnicity.
- These findings provide a basis for further research into ethnic variations of drug transporters and their clinical implications.
