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Basolateral Efflux Mediated by Multidrug Resistance-Associated Protein 3 (Mrp3/ Abcc3) Facilitates Intestinal Absorption of Folates in Mouse.
- Source :
-
Pharmaceutical Research . Apr2010, Vol. 27 Issue 4, p665-672. 8p. 2 Charts, 5 Graphs. - Publication Year :
- 2010
-
Abstract
- This study investigated the role of an ABC transporter, Mrp3/ Abcc3 in intestinal folate absorption. Plasma concentrations of folic acid and leucovorin, given orally, were determined in wild-type and Mrp3 −/− mice. Mucosal-to-serosal transport was determined in the everted intestinal sacs. The plasma concentrations of endogenous 5-methyltetrahydrofolic acid, homocysteine and vitamin B12, and mRNA levels of hepatic and intestinal folate metabolizing enzymes were compared between wild-type and Mrp3 −/− mice. C max and area-under plasma concentration–time curve of folic acid were 3.0- and 2.3-fold lower in Mrp3 −/− mice compared with wild-type mice, whereas the total body clearance was unchanged. Absorption of leucovorin was significantly delayed in Mrp3 −/− mice. Mucosal-to-serosal transport of folic acid and leucovorin was significantly decreased in the duodenum of Mrp3 −/− mice, where their PS serosal was decreased to 6.3 and 22% of that in wild-type mice, respectively. PS serosal of 5-methyltetrahydrofolic acid was moderately decreased in Mrp3 −/− mice. There was no obvious abnormality in folate homeostasis in Mrp3 −/− mice. Mrp3 accounts for the serosal efflux of folic acid and leucovorin, while it makes a moderate contribution to the serosal efflux of 5-methyltetrahydrofolic acid in mice. Mrp3 dysfunction does not disrupt folate homeostasis in mouse. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 07248741
- Volume :
- 27
- Issue :
- 4
- Database :
- Academic Search Index
- Journal :
- Pharmaceutical Research
- Publication Type :
- Academic Journal
- Accession number :
- 48536798
- Full Text :
- https://doi.org/10.1007/s11095-009-0047-4