uu.seUppsala University Publications
Change search
ReferencesLink to record
Permanent link

Direct link
Cytochromes P450 and MDR1 mRNA expression along the human gastrointestinal tract
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Centre for Clinical Research, County of Västmanland. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Sciences, Gastroenterology/Hepatology.
Show others and affiliations
2005 (English)In: British Journal of Clinical Pharmacology, ISSN 0306-5251, E-ISSN 1365-2125, Vol. 60, no 1, 54-60 p.Article in journal (Refereed) Published
Abstract [en]


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.


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.


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).


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.

Place, publisher, year, edition, pages
2005. Vol. 60, no 1, 54-60 p.
Keyword [en]
Adult, Aged, Aryl Hydrocarbon Hydroxylases/*metabolism, Cytochrome P-450 CYP3A, Female, Gastrointestinal Tract/*metabolism, Genes; MDR, Humans, Intestinal Mucosa/metabolism, Male, Middle Aged, Oxidoreductases; N-Demethylating/*metabolism, RNA; Messenger/*metabolism, Research Support; Non-U.S. Gov't, Reverse Transcriptase Polymerase Chain Reaction/methods
National Category
Medical and Health Sciences
URN: urn:nbn:se:uu:diva-93030DOI: 10.1111/j.1365-2125.2005.02389.xPubMedID: 15963094OAI: oai:DiVA.org:uu-93030DiVA: diva2:166382
Available from: 2005-05-09 Created: 2005-05-09 Last updated: 2013-03-22Bibliographically approved
In thesis
1. Qualitative and Quantitative Assessment of Cytochromes P450 mRNA in Human: Studies in the Liver, Blood and Gastrointestinal Mucosa
Open this publication in new window or tab >>Qualitative and Quantitative Assessment of Cytochromes P450 mRNA in Human: Studies in the Liver, Blood and Gastrointestinal Mucosa
2005 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Drugs and other foreign compounds must often be metabolised before they can be excreted from the body. One enzyme system that is responsible for this is the cytochrome P450 gene family (CYP). In this thesis, new sensitive molecular techniques have been used to study the human gene expression of some CYP enzymes, as well as the P-glycoprotein transporter (P-gp). The aim was to evaluate whether tissues other than the liver, e.g. the blood, could be used to assess an individual's drug metabolic capacity. Another aim was to investigate the gene expression in relation to the liver transplant process and a third aim was to evaluate the expression in gastrointestinal mucosa in both normal and inflamed mucosa.

We evaluated the CYP gene expression in paired specimens of liver and blood but found no correlation in the expression patterns of these two tissues. Instead, we found the opposite pattern, where, for example, CYP1B1 had the highest expression in the blood but the lowest in the liver and CYP2E1 was the enzyme with the highest expression in the liver. In an investigation of the expression of four different CYP enzymes and P-gp in liver transplants before and during the first year after transplantation, we found that the levels of all the CYP enzymes but not P-gp increased with time. We also found that the expression of CYP3A4 was inversely related to the normalised plasma levels of the immunosuppressive drugs cyclosporine and tacrolimus.

In the gastrointestinal tract, CYP2E1 was the enzyme with the highest mRNA expression compared with CYP3A4, CYP3A5 and the transporter P-gp. CYP3A4 has its highest expression in the duodenum compared with the expression in the stomach and the colon. CYP3A5 is expressed at a higher level than CYP3A4 in the colon. P-gp expression levels increase through the gastrointestinal tract to the left colon. Gene expression levels of CYP2E1 and CYP3A4 decrease in severely inflamed rectal mucosa.

In conclusion, this is a sensitive method for studying gene activity in a clinical situation, even though at this point we are not able to use blood or gastrointestinal mucosa as “surrogate” tissue to estimate an individual’s drug metabolic capacity. The studies in liver transplants and gastrointestinal mucosa are unique in that the gene expression is investigated during a clinical course of events.

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2005. 57 p.
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 37
Medical sciences, cytochrome P450, CYP1A2, CYP1B1, CYP2E1, CYP3A4, CYP3A5, P-gp, gene expression, RT-PCR, liver, blood, gastrointestinal mucosa, MEDICIN OCH VÅRD
National Category
Medical and Health Sciences
urn:nbn:se:uu:diva-5786 (URN)91-554-6245-6 (ISBN)
Public defence
2005-05-30, Samlingssalen, Ing. 29 Centrallasarettet, Västerås, 13:15
Available from: 2005-05-09 Created: 2005-05-09Bibliographically approved

Open Access in DiVA

No full text

Other links

Publisher's full textPubMed
By organisation
Centre for Clinical Research, County of VästmanlandGastroenterology/Hepatology
In the same journal
British Journal of Clinical Pharmacology
Medical and Health Sciences

Search outside of DiVA

GoogleGoogle Scholar
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 226 hits
ReferencesLink to record
Permanent link

Direct link