Expression of multidrug resistance-associated protein 2 in small intestine from pregnant and postpartum rats

Abstract

We analyzed the expression of multidrug resistance-associated protein 2 (mrp2) in the small intestine of control female rats and in rats during late pregnancy (19-20 days of pregnancy) and lactation (2-4, 10-14, and 21 days after delivery). Western blot analysis was performed on brush-border membranes prepared from different regions of the small intestine. Expression of mrp2 was maximal in the proximal segments for all experimental groups, was preserved in pregnant rats, and increased by 100% in postpartum rats by late lactation with respect to control animals. Northern blot analysis of mrp2 mRNA revealed a positive correlation with protein levels. Transport of S-glutathione-dinitrophenol (DNP-SG) from the intestinal cell to the lumen was analyzed in the everted intestinal sac model. Secretion of DNP-SG was not altered in pregnant rats but increased in lactating animals by late lactation. Intestinal mrp2 mRNA, protein, and transport activity are increased in lactating rats, suggesting that this may represent an adaptive mechanism to minimize the toxicity of dietary xenobiotics in response to increased postpartum food consumption.

Absorption and Metabolism of Flavonoids in the Caco-2 Cell Culture Model and a Perused Rat Intestinal Model

“…We hypothesized that MRP2 is involved in the excretion of phase II isoflavone conjugates. This is supported by the fact that the recovery pattern of genistein conjugate in the rat small intestine agrees with the expression pattern of MRP2, which has the highest expression level in jejunum and lowest in the terminal ileum (Mottino et al, 2001). It is also supported by the fact that the addition of 100 M verapamil (a potent p-glycoprotein inhibitor) to the jejunal perfusate did not change the recovery pattern of glucuronide metabolites (data not shown).…”

The MRP family of drug efflux pumps

“…In spite of the similarity in substrate range, the functions of MRP2 in the body are distinct from those of MRP1 as a result of differences in expression pattern and subcellular polarity. In contrast to MRP1, MRP2 assumes apical localization in polarized cells (Figure 2), and it is mainly expressed in liver canaliculi, with lower levels in renal proximal tubules, gut enterocytes, syncytiotrophoblast cells of the placenta and possibly brain capillaries (Kartenbeck et al, 1996;Schaub et al, 1997;Miller et al, 2000;Mottino et al, 2000;St-Pierre et al, 2000). Therefore, it is functionally similar to Pgp in its involvement in the terminal elimination of compounds and its role as a barrier in gut and placenta.…”

Effect of Glucagon-Like Peptide 2 on Hepatic, Renal, and Intestinal Disposition of 1-Chloro-2,4-dinitrobenzene

“…In support of this possibility, we observed less intrahepatic accumulation of DNP-SG in GLP-2 group than in controls, as detected 5 min after CDNB administration (Table 1). Mrp2-mediated transport, rather than GST conjugation, is the probable rate-limiting step in the overall disposition of CDNB in intestine (Mottino et al, 2001). However, the situation could be different in other tissues with high constitutive Mrp2 expression such …”

“…Their volumes were estimated gravimetrically. DNP-SG and DNP-CG content was assessed in all samples by high-performance liquid chromatography, as described previously (Mottino et al, 2001). Saline was administered intravenously throughout the experiment to replenish body fluids.…”

“…In a different set of rats, the animals were sacrificed by exsanguinations 5 min after administration of CDNB, and the liver, proximal jejunum, and kidneys were removed, rinsed with ice-cold saline, and homogenized in two volumes of PBS, pH 7.35. DNP-SG was determined in serum as well as in liver, jejunum, and renal cortex homogenates (Mottino et al, 2001). Glutathione-conjugating activity toward CDNB was assayed in vitro in cytosol from liver, jejunum, and renal cortex by a reported procedure (Catania et al, 2000).…”