Gene and Protein Expression of P-Glycoprotein, MRP1, MRP2, and CYP3A4 in the Small and Large Human Intestine

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• 作者：Sofia Berggren ; Christine Gall ; Nadine Wollnitz ; Mats Ekelund ; Urban Karlbom ; Janet Hoogstraate ; Dieter Schrenk ; Hans Lennern&auml ; s
• 刊名：Molecular Pharmaceutics
• 出版年：2007
• 出版时间：April 2007
• 年：2007
• 卷：4
• 期：2
• 页码：252 - 257
• 全文大小：111K
• 年卷期：v.4,no.2(April 2007)
• ISSN：1543-8392

文摘

The cytochrome P450 3A4 enzyme and the ABC-transporters may affect the first-pass extraction and bioavailability of drugs and metabolites. Conflicting reports can be found inthe literature on the expression levels of efflux transporters in human intestine and how theyvary along the intestine. The relative levels of mRNA and protein of CYP3A4 and the ABCtranporters Pgp (ABCB1), MRP1 (ABCC1), and MRP2 (ABCC2) were determined using RT-PCR and Western blot for human intestinal tissues (n = 14) from jejunum, ileum and colon.The expression of mRNA for CYP3A4, Pgp, and MRP2 was highest in jejunum and decreasedtoward more distal regions, whereas MRP1 was equally distributed in all intestinal regions. ForCYP3A4, a more significant correlation could be established between mRNA and proteinexpression than for the ABC transporters. The samples showed considerable interindividualvariability, especially at the protein level. The apically located Pgp and MRP2 showed a similarexpression pattern along the human intestine as for CYP3A4. The gene expression of MRP1exhibited a more uniform distribution.