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MUCOSAL BIOLOGY

ATP-dependent transport of organic anions into isolated basolateral membrane vesicles from rat intestine

Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan

Submitted 7 February 2003 ; accepted in final form 9 June 2004

The mechanism for the cellular extrusion of organic anions across the intestinal basolateral membrane was examined using isolated membrane vesicles from rat jejunum, ileum, and colon. It was found that 17-estradiol 17-D-glucuronide (E₂17G) is taken up in an ATP-dependent manner into the basolateral membrane vesicles (BLMVs) but not into the brush-border or microsomal counterparts. The ATP-dependent uptake of E₂17G into BLMVs from jejunum and ileum was described by a single component with a K_m value of 23.5 and 8.31 µM, respectively, whereas that into the BLMVs from colon was described by assuming the presence of high (K_m = 0.82 µM)- and low-affinity (K_m = 35.4 µM) components. Taurocholate, 6-hydroxy-5,7-dimethyl-2-methylamino-4-(3-pyridylmethyl) benzothiazole glucuronide and taurolithocholate sulfate, but not leukotriene C₄, were significantly taken up by the BLMVs. In addition to such substrate specificity, the inhibitor sensitivity of the ATP-dependent transport in BLMVs was similar to that of rat multidrug resistance-associated protein 3 (Mrp3), which is located on the basolateral membrane of enterocytes. Together with the fact that the rank order of the extent of the expression of Mrp3 (jejunum < ileum << colon) is in parallel with that of the extent of the transport of ligands, these results suggest that the ATP-dependent uptake of organic anions into isolated intestinal BLMVs is at least partly mediated by Mrp3.

intestinal transport; basolateral membrane; organic anion transport; bile acid transport; multidrug resistance-associated protein

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