Received for publication February 7, 2008.
Revised March 28, 2008.
Accepted for publication March 28, 2008.

Closing the gaps - A full-scan of the intestinal expression of Pgp, Bcrp and Mrp2 in male and female rats

Abstract

Intestinal ABC transporters may affect the bioavailability and effectiveness of orally administered drugs. Available studies on regional expression of intestinal efflux transporters were done with selected intestinal segments only and inconsistent with regard to the variability of transporter expression and the course of expression along the intestine. For an evaluation of the consistency between mRNA and protein expression, relative expression levels of Pgp (ABCB1), Bcrp (ABCG2) and Mrp2 (ABCC2) were determined using qRT-PCR and Western blot in rat intestinal segments from duodenum, jejunum, ileum and colon. In addition, the protein expression of Pgp, Bcrp and Mrp2 from the entire rat intestine was studied by a complete 3 cm segmentation in order to evaluate the predictive power of expression analyses from selected intestinal segments. Pgp showed an increase from proximal to distal regions, and Bcrp an arcuate pattern with highest expression towards the end of small intestine, and Mrp2 decreased along the intestinal axis from proximal to distal parts. No gender specific differences could be observed. Regarding the concordance of mRNA and protein expression Pgp and Bcrp mRNA samples allow good estimations about the corresponding protein expression (for Pgp limited to the mdr1a isoform) but for Mrp2 pronounced deviation could be observed. All transporters showed considerable intra- and interindividual variability, especially at the protein level making it problematic to take transporter expressions of small sections exemplary for general assumptions on intestinal abundances.

Key words: ABC transporters, absorption, drug absorption, intestinal bioavailability, intestinal transport, p-glycoprotein