Basolateral efflux mediated by multidrug resistance-associated protein 3 (Mrp3/Abcc3) facilitates intestinal absorption of folates in mouse.
Pharm Res
; 27(4): 665-72, 2010 Apr.
Article
em En
| MEDLINE
| ID: mdl-20148291
ABSTRACT
PURPOSE:
This study investigated the role of an ABC transporter, Mrp3/Abcc3 in intestinal folate absorption.METHODS:
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 B(12), and mRNA levels of hepatic and intestinal folate metabolizing enzymes were compared between wild-type and Mrp3 ( -/- ) mice.RESULTS:
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.CONCLUSIONS:
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Associadas à Resistência a Múltiplos Medicamentos
/
Ácido Fólico
/
Absorção Intestinal
Tipo de estudo:
Risk_factors_studies
Limite:
Animals
Idioma:
En
Revista:
Pharm Res
Ano de publicação:
2010
Tipo de documento:
Article
País de afiliação:
Japão