title: Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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 < 0.000001).
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre of Clinical Research, Uppsala University, Central Hospital, Västerås, Sweden. mari.thorn@telia.com
authors.forename: Mari
authors.initials: M
authors.lastname: Thörn
authors.forename: Niklas
authors.initials: N
authors.lastname: Finnström
authors.forename: Stefan
authors.initials: S
authors.lastname: Lundgren
authors.forename: Anders
authors.initials: A
authors.lastname: Rane
authors.forename: Lars
authors.initials: L
authors.lastname: Lööf
mesh_terms: D000328:Adult; D000368:Aged; D001189:Aryl Hydrocarbon Hydroxylases / Q000378:metabolism*; D051544:Cytochrome P-450 CYP3A; D005260:Female; D041981:Gastrointestinal Tract / Q000378:metabolism*; D019450:Genes, MDR; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D010089:Oxidoreductases, N-Demethylating / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods
chemical_list: D012333:RNA, Messenger; D001189:Aryl Hydrocarbon Hydroxylases; D051544:Cytochrome P-450 CYP3A; D010089:Oxidoreductases, N-Demethylating