Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse.
Abstract: The gene and protein expression and the cellular localization of the ABC transport proteins breast cancer resistance protein (BCRP), multidrug resistance-associated protein 1 (MRP1) and multidrug resistance-associated protein 2 (MRP2) have been examined in the intestines, liver and kidney in horse. High gene and protein expression of BCRP and MRP2 were found in the small intestines, with cellular localization in the apical membranes of the enterocytes. In the liver, MRP2 was present in the bile canalicular membranes of the hepatocytes, whereas BCRP was localized in the cytoplasm of hepatocytes in the peripheral parts of the liver lobuli. In the kidney both BCRP and MRP2 were predominantly present in the distal tubuli and in the loops of Henle. In most tissues, the gene and protein expression of MRP1 were much lower than for BCRP and MRP2. Immunostaining of MRP1 was detectable only in the intestines and with localization in the cytoplasm of enterocytes in the caecum and colon and in the cells of serous acini of Brunner's glands in the duodenum and the upper jejunum. The latter cells were also stained for BCRP, but not for MRP2. Many drugs used in horse are substrates for one or more of the ABC transport proteins. These transporters may therefore have important functions for oral bioavailability, distribution and excretion of substrate compounds in horse.
Publication Date: 2010-07-22 PubMed ID: 20646193DOI: 10.1111/j.1365-2885.2009.01140.xGoogle Scholar: Lookup
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- Comparative Study
- Journal Article
- Research Support
- Non-U.S. Gov't
Summary
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The research examines the gene and protein expression and cellular location of certain proteins in horse intestines, liver, and kidneys and suggests that these proteins may significantly affect the horse’s distribution and excretion of drugs.
Gene and Protein Expression
- The study focuses on the expression and localization of ABC transport proteins, particularly BCRP, MRP1, and MRP2, within horse intestines, liver, and kidney tissues.
- The researchers found high gene and protein expression of BCRP and MRP2 in the small intestines of horses, more specifically, on the apical membranes of the enterocytes (cells lining the intestine).
- Comparatively, in most tissues, the gene and protein expression of MRP1 were much lower than for BCRP and MRP2.
Localization in Liver and Kidneys
- Within the liver, MRP2 was localized on the bile canalicular membranes of the hepatocytes (liver cells), with BCRP identified in the cytoplasm of hepatocytes in the peripheral parts of the liver lobuli (small division of a liver).
- Both BCRP and MRP2 proteins were predominantly present in the distal tubuli and in the loops of Henle within the kidneys.
Localization in Intestines and Implications
- MRP1 was only detectable in the intestines and was located in the enterocytes’ cytoplasm in the caecum and colon, and in the cells of Brunner’s glands in the duodenum and the upper jejunum. The cells of Brunner’s glands also stained for BCRP, but not for MRP2.
- The finding is of significance as many drugs used in horses are handled by these ABC transport proteins.
- Given the proteins’ function in bioavailability, distribution, and excretion, understanding their expression and location could have important implications for horse drug therapy, potential side effects, and drug efficacy.
Cite This Article
APA
Tydén E, Bjornstrom H, Tjälve H, Larsson P.
(2010).
Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse.
J Vet Pharmacol Ther, 33(4), 332-340.
https://doi.org/10.1111/j.1365-2885.2009.01140.x Publication
Researcher Affiliations
- Department of Biomedical Sciences and Veterinary Public Health, Division of Pathology, Pharmacology and Toxicology, Swedish University of Agricultural Sciences, Uppsala, Sweden. eva.tyden@bvf.slu.se
MeSH Terms
- ATP-Binding Cassette Transporters / genetics
- ATP-Binding Cassette Transporters / metabolism
- Animals
- DNA Primers
- Dogs
- Female
- Horses
- Humans
- Immunohistochemistry / veterinary
- Intestinal Mucosa / metabolism
- Kidney / metabolism
- Liver / metabolism
- Male
- Membrane Proteins / genetics
- Membrane Proteins / metabolism
- Multidrug Resistance-Associated Protein 2
- Multidrug Resistance-Associated Proteins / genetics
- Multidrug Resistance-Associated Proteins / metabolism
- Rats
- Reverse Transcriptase Polymerase Chain Reaction / veterinary
- Sweden
Citations
This article has been cited 3 times.- Rosa B. Equine Drug Transporters: A Mini-Review and Veterinary Perspective. Pharmaceutics 2020 Nov 8;12(11).
- Tong WY, Alnakhli M, Bhardwaj R, Apostolou S, Sinha S, Fraser C, Kuchel T, Kuss B, Voelcker NH. Delivery of siRNA in vitro and in vivo using PEI-capped porous silicon nanoparticles to silence MRP1 and inhibit proliferation in glioblastoma. J Nanobiotechnology 2018 Apr 13;16(1):38.
- Collaco AM, Jakab RL, Hoekstra NE, Mitchell KA, Brooks A, Ameen NA. Regulated traffic of anion transporters in mammalian Brunner's glands: a role for water and fluid transport. Am J Physiol Gastrointest Liver Physiol 2013 Aug 1;305(3):G258-75.
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