Changes in mRNA expression of ABC and SLC transporters in liver and intestines of the adjuvant‐induced arthritis rat

Abstract

In this study, a real-time reverse transcription-polymerase chain reaction was used to determine the effects of adjuvant-induced arthritis (AA) on the amounts of mRNA of 12 types of rat ATP-binding cassette (ABC) and solute carrier (SLC) transporters in the liver and small intestine, 7 (D7) and 21 days (D21) after the injection of adjuvant. There were no significant differences in mRNA levels of ABC and SLC transporters between the livers of AA and control rats on D7, except in the case of Mdr1a. However, levels of Mdr1a, Mrp2 and Oatp SLC transporters were significantly lower in AA than in the control livers on D21. In contrast, the mRNA levels of several ABC and SLC transporters, especially Mrp2, Bcrp, LAT2 and Oatp1a5, were significantly lower in the small intestines of AA rats compared with the controls on D7, though there were no significant differences by D21. The time-dependent alterations in mRNA levels of the pregnane X receptor, but not the constitutive androstane receptor, in the liver and intestine were similar to the changes in mRNA levels of most transporters examined. The present study showed that AA was associated with reduced mRNA expression of several ABC and SLC transporters in the liver and small intestine, but that the time courses of the effects of AA on mRNA expression differed between the liver and small intestine. These results raise the possibility of a functional change of the transporters of liver and intestine in AA rats.

Intestinal Absorption of HMG-CoA Reductase Inhibitor Pravastatin Mediated by Organic Anion Transporting Polypeptide

“…Although pravastatin has been shown to be transported by human OATP2B1 in a pH-sensitive manner, little information is available about whether or not influx and efflux transporters are involved in pravastatin absorption in vivo. In the present study, we focused on rat Oatp1a5 to evaluate the impact of OATP/Oatp on the intestinal absorption of pravastatin, because Oatp1a5 is the only Oatp transporter that is known to be expressed at the apical membranes in rat small intestine (25)(26)(27). Here, we show, by means of in situ and in vivo experimental techniques, that Oatp1a5, but not Mdr1 or Bcrp, contributes to the intestinal absorption of pravastatin in vivo.…”

“…intestinal epithelial cells remains obscure (25)(26)(27). Therefore, in the present study, we focused on rat Oatp1a5, which is expressed at the apical membrane, as an influx transporter for pravastatin involved in its intestinal absorption in rats (25).…”

Differential Effect of Grapefruit Juice on Intestinal Absorption of Statins Due to Inhibition of Organic Anion Transporting Polypeptide and/or P-glycoprotein

“…Using rats as an experimental model, we focused on Oatp1a5 and Oatp2b1 to evaluate the contribution of Oatp family members to the GFJ interaction with these statins because Oatp1a5 and Oatp2b1 are expressed in rodent small intestine at relatively high levels. [22][23][24][25] Rat Oatp1a5 and Oatp2b1 share high sequence homology with human OATP1A2 and OATP2B1, respectively. Therefore, our results also provide a rationale for understanding the contributions of OATP and/or P-gp to the differential effect of GFJ on the intestinal absorption of pravastatin and pitavastatin in humans.…”

Regulation of hepatic ABCC transporters by xenobiotics and in disease states

“…Mrp2 expression does not change during acute liver injury in rats induced by treatment with carbon tetrachloride, possibly due to the unchanged binding activity of RXRα:RARα in the Mrp2 gene (Geier et al, 2002b). Time-dependent alterations in PXR mRNA levels are similar to those for Mrp2 in rats with adjuvant-induced arthritis (Uno et al, 2009). Using partial regression analysis, CAR, HNF-4-α, and PXR are associated with human liver MRP2 gene expression (Wortham et al, 2007).…”

“…In female Lewis or SD rats with arthritis induced by adjuvant Mycobacterium butyricum , liver Mrp2 expression decreases (Achira et al, 2002; Uno et al, 2009). …”