Previous studies have shown that 1α,25-dihydroxyvitamin D3 (1,25(OH)2D3) treatment (2.56 nmol/kg i.p. daily×4) increased PepT1, Mrp2, Mrp4, Asbt, but not Mdr1/P-gp in the rat small intestine. In this study, the intestinal everted sac technique, together with various select probes: mannitol (paracellular transport), glycylsarcosine (PepT1), 5(and 6)-carboxy-2',7'-dichlorofluorescein (CDF) diacetate (precursor of CDF for Mrp2), adefovir dipivoxil (precursor of adefovir for Mrp4) and digoxin (P-gp) was used to examine the functional changes of these transporters. After establishing identical permeabilities (Papp) of mannitol for the apical-to-basolateral (A-to-B) and basolateral-to-apical (B-to-A) directions at 20 min in 1,25(OH)2D3-treated vs. vehicle-treated duodenal, jejunal and ileal everted sacs, a significant enhancement of net A-to-B transport of glycylsarcosine in the duodenum, increased B-to-A transport of CDF and A-to-B and B-to-A transport of adefovir in the jejunum were observed with 1,25(OH)2 D3 treatment. However, the A-to-B and B-to-A transport of digoxin in the ileum was unchanged. These changes in transporter function in the rat intestinal everted sac corresponded well to changes in proteins that were observed previously. This study confirms that the rat intestinal PepT1, Mrp2 and Mrp4, but not P-gp are functionally induced by 1,25(OH)2D3 treatment via the vitamin D receptor (VDR).
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