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.

Human Intestinal PEPT1 Transporter Expression and Localization in Preterm and Term Infants

“…MDR1 was stained at the apical border of the enterocyte, similar to MDR1 staining in 59 duodenal biopsies from infants up to 7 years of age and from fetuses from a gestational age of 16 and 20 weeks (van Kalken et al, 1992;Fakhoury et al, 2005). MRP2 apical staining matches staining in human colorectal cancer tissue as well as intestinal tissue from horse, rabbits, and rats (Mottino et al, 2000;Van Aubel et al, 2000;Tydén et al, 2010), and intraepithelial OATP2B1 staining at the basolateral enterocyte border was similar to staining in human colonic biopsies from adults (Kleberg et al, 2012). The localization corresponds to the function of MDR1, MRP2, and PEPT1 in facilitating uptake of substrates in the enterocyte, whereas OATP2B1 facilitates excretion from the enterocyte to blood (Klaassen and Aleksunes, 2010).…”

Clarithromycin Is Absorbed by an Intestinal Uptake Mechanism That Is Sensitive to Major Inhibition by Rifampicin: Results of a Short-Term Drug Interaction Study in Foals

“…Pharmacokinetic studies in foals are suitable for predicting transporter variability in human beings, because the foals' body size enables noninvasive experimental procedures, because protein homology and expression of drug transporters in horses are similar to those in rodents and humans, and because protein expression is regulated at a transcriptional level (Tydén et al, 2009(Tydén et al, , 2010. CLR and RIF are components of treatment protocols for eradication of Rhodococcus equi, which causes severe necrotizing pneumonia, with high mortality rates, in foals (Giguère et al, 2004).…”

Expression and subcellular localization of efflux transporter ABCG2/BCRP in important tissue barriers of lactating dairy cows, sheep and goats

“…Slides were then blocked in 5% normal goat serum in PBS (blocking buffer) for 1 h at room temperature. To obtain comparable data, we used the monoclonal antibody BXP‐21 just as it was applied in human (Maliepaard et al ., ), porcine (Schrickx, ) and equine (Tydén et al ., ) tissue sections. Additionally, BXP‐53 monoclonal antibody was used for staining of mammary gland as applied by Jonker et al .…”

“…Human BCRP is known to be localized apically in epithelial plasma membranes of small intestine, colon, hepatic bile canaliculi, placenta, mammary gland (Maliepaard et al ., ; Jonker et al ., ), lung (Scheffer et al ., ) and kidney (Schrickx, ; Huls et al ., ). This carrier protein is also expressed on the luminal surface of blood vessels (Maliepaard et al ., ; Schrickx, ; Tydén et al ., ). Thus, BCRP is suggested to play a cytoprotective role (Staud & Pavek, ; Sarkadi et al ., ) and limits oral bioavailability by counteracting xenobiotic transfer in important tissue barriers (Van Herwaarden & Schinkel, ; Vlaming et al ., ).…”