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Drug Metabolism and Disposition Fast Forward
First published on March 10, 2008; DOI: 10.1124/dmd.107.019687

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Received for publication November 8, 2007.
Revised February 28, 2008.
Accepted for publication March 5, 2008.

Characterization of Cytochrome P450 protein expression along the entire length of the intestine of male and female rats

Doreen Mitschke 1*, Andreas Reichel 1, Gert Fricker 2, Ursula Moenning 1

1 Bayer Schering Pharma AG 2 University of Heidelberg

* Address correspondence to: E-mail: doreen.mitschke{at}bayerhealthcare.com

Abstract

Intestinal CYP P450 proteins play an important role in the biotransformation of drugs and may significantly limit their oral absorption and bioavailability. Therefore, we have investigated the amount of CYP P450 proteins via Western blot analysis along the entire intestine of male and female rats. Despite of the use of an inbred rat strain, controlled housing conditions for the animals and a timed sample preparation, high interindividual differences in the expression of all CYP P450 proteins was observed. CYP3A (135 to 243 fmol/mg protein) and CYP2B1 (107-645fmol/mg protein) were the most abundant CYP P450 isoforms in the duodenum and jejunum of rat intestine, but were neither present in the ileum nor in the colon. Compared to CYP2B1 and CYP3A, CYP2D1 (25-71fmol/mg protein) and CYP2C6 (3-10fmol/mg protein) were only expressed in minor amounts. CYP2C11 could not be identified in the entire rat intestine. In conclusion, this is the first systematic evaluation and quantification of the expression of CYP P450 proteins along the entire length of the intestine in the rat both male and female. This data will provide a basis for a better understanding of the extent of intestinal metabolism along the gastrointestinal tract.


Key words: CYP expression, cytochrome P450, extrahepatic cytochrome P450, gastrointestinal cytochrome P450


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Closing the Gaps: A Full Scan of the Intestinal Expression of P-Glycoprotein, Breast Cancer Resistance Protein, and Multidrug Resistance-Associated Protein 2 in Male and Female Rats
Drug Metab. Dispos., July 1, 2008; 36(7): 1249 - 1254.
[Abstract] [Full Text] [PDF]


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