Expression and localization of BCRP, MRP1 and MRP2 in intestines, liver and kidney in horse.
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.
Tydén
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E
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
Bjornstrom
H
H
Tjälve
H
H
Larsson
P
P
D018528:ATP-Binding Cassette Transporters / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D017931:DNA Primers; D004285:Dogs; D005260:Female; D006736:Horses; D006801:Humans; D007150:Immunohistochemistry / Q000662:veterinary; D007413:Intestinal Mucosa / Q000378:metabolism*; D007668:Kidney / Q000378:metabolism*; D008099:Liver / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics* / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000662:veterinary; D013548:Sweden
D018528:ATP-Binding Cassette Transporters; D017931:DNA Primers; D008565:Membrane Proteins; D000089762:Multidrug Resistance-Associated Protein 2; D027425:ATP-Binding Cassette, Sub-Family C Proteins; C000715087:ABCC2 protein, human; C421109:multidrug resistance-associated protein 1