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Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract
Author(s) -
Thörn Mari,
Finnström Niklas,
Lundgren Stefan,
Rane Anders,
Lööf Lars
Publication year - 2005
Publication title -
british journal of clinical pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.216
H-Index - 146
eISSN - 1365-2125
pISSN - 0306-5251
DOI - 10.1111/j.1365-2125.2005.02389.x
Subject(s) - duodenum , cyp3a4 , gastrointestinal tract , cyp3a5 , biology , messenger rna , stomach , gene expression , cyp3a , cecum , microbiology and biotechnology , real time polymerase chain reaction , medicine , gene , endocrinology , cytochrome p450 , genetics , metabolism , biochemistry , genotype
Aim The aim of this study was to quantify the mRNA expression of three cytochromes P450 (CYP) and P‐glycoprotein (P‐gp) in the human gastrointestinal (GI) tract. Method Biopsies were obtained from gastric, duodenal, colonic and rectal mucosa during routine gastro‐colonoscopy in 27 patients. The biopsies were snap‐frozen in liquid nitrogen. Real‐time reverse transcriptase‐polymerase chain reaction (RT‐PCR) was used for the quantitative analyses of mRNA expressed by the CYP2E1, CYP3A4 and CYP3A5 genes, and the MDR1 gene coding for P‐gp protein. The mRNA expression of b‐actin was used as an internal standard for comparisons between samples. Results All CYP genes were expressed at all locations throughout the GI tract, although all showed substantial interindividual variation. CYP2E1 had the highest expression at all locations ( P < 0.05 to P < 0.0001), except in the right colon. CYP3A4 and CYP3A5 had their highest mRNA expression in the duodenum ( P < 0.001 and P < 0.000 001, respectively) and CYP2E1 in the stomach ( P < 0.01). MDR1 mRNA concentrations increased along the GI tract with the highest expression being in the left colon ( P < 0.1) .Conclusion Multiple sampling within the same individual enabled us to study the intraindividual variation in expression of CYP and MDR1 genes along the GI tract. We find that CYP2E1 mRNA expression is higher than that of the other CYPs . CYP3A expression is highest in the duodenum and that of MDR1 increases from stomach and duodenum to colon.