Effect of Pregnenolone 16α-Carbonitrile on the Expression of P-Glycoprotein in the Intestine, Brain and Liver of Mice.
Biol Pharm Bull
; 41(6): 972-977, 2018.
Article
em En
| MEDLINE
| ID: mdl-29863087
ABSTRACT
P-Glycoprotein (P-gp), encoded by the MDR1 (ABCB1) gene in humans and by Mdr1a and Mdr1b genes in rodents, is a member of the superfamily of ATP-binding cassette transporters. Since P-gp is constitutively expressed in numerous tissues and exhibits a broad specificity in substrate recognition, it can play a crucial role in limiting the absorption and distribution of xenobiotics by decreasing their intracellular accumulation. The expression of P-gp is regulated by various nuclear receptors such as pregnane X receptor (PXR). Although the characterization of P-gp induction by PXR ligands is a crucial goal for predicting pharmacokinetics of drugs, findings regarding the induction of P-gp by PXR ligands in vivo are still controversial. In this study, we examined the effect of pregnenolone 16α-carbonitrile (PCN), a murine PXR ligand, on the expression of Mdr1a/1b mRNA and P-gp protein in the intestine, brain and liver of mice. The results showed that PCN increased the expression of both Mdr1a/1b mRNA and P-gp protein in the intestine and the brain. The present study provided the first evidence that P-gp is inducible by PCN in the large intestine. The results also showed that P-gp protein was induced by PCN in the cortex but not in the whole brain. On the other hand, PCN increased the expression of Mdr1a/1b mRNA in the liver, although no increase was observed in the expression of P-gp protein. These results suggested different effect of PCN on the expression of P-gp protein in the intestine, brain and liver of mice.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Carbonitrila de Pregnenolona
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Encéfalo
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Subfamília B de Transportador de Cassetes de Ligação de ATP
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Intestinos
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Fígado
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Biol Pharm Bull
Assunto da revista:
BIOQUIMICA
/
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article
País de publicação:
JAPAN
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JAPON
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JAPÃO
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JP