Differences between nuclear run-off and mRNA levels for multidrug resistance gene expression in the cephalocaudal axis of the mouse intestine

Chianale, José; Vollrath, Valeska; Wielandt, Ana María; Miranda, Soledad; Gonzalez, Robinson G.; Fresno, Aria M.; Quintana, Carlos; González, Sergio; Andrade, Leonardo R.; Guzmán, S

doi:10.1016/0167-4781(95)00179-4

Cited by 28 publications

(21 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…However, other studies have observed an apparent expression peak in the ileum (Trezise et al, 1992;Chianale et al, 1995) but did not suggest a second PGP expression peak in the distal colon like that reported here. There have been relatively few studies of regional PGP transporter activity, arguably a more reliable measure.…”

contrasting

confidence: 50%

“…Several studies have noted significant regional differences in PGP expression at the mRNA level with expression increasing from the small intestine to the colon (Fojo et al, 1987;Fricker et al, 1996;Li et al, 1999). However, other studies have reported a different distribution (Cordon-Cardo et al, 1990;Chianale et al, 1995), which may in part be due to species differences in transporter expression. It is also noteworthy that little work has been done to examine regional variation of any transporter within the large intestine, a physiologically important site for xenobiotic efflux (Penny and Campbell, 1994).…”

mentioning

confidence: 87%

“…There have been relatively few studies of regional PGP transporter activity, arguably a more reliable measure. In vitro measurements of drug efflux along the rat intestine have suggested peak PGP activity in ileum with lower levels in upper small intestine and colon (Chianale et al, 1995;Yumoto et al, 1999;Kunta et al, 2000;Stephens et al, 2001). The present study, utilizing a more unequivocal measure of PGP-mediated drug transport using mdr1a(Ϫ/Ϫ) mouse intestine, offers clear evidence that PGP-mediated activity increases markedly from jejunum to ileum.…”

mentioning

confidence: 99%

See 2 more Smart Citations

Region-Dependent Modulation of Intestinal Permeability by Drug Efflux Transporters: In Vitro Studies in mdr1a(−/−) Mouse Intestine

Stephens

Tanianis-Hughes

Higgs

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

Information on the extent to which xenobiotics interact with P-glycoprotein (PGP) during transit through the intestine is crucial in determining the influence of PGP on oral drug absorption. We have recently described a novel use of isolated ileum from PGP-deficient mdr1a(Ϫ/Ϫ) mice to resolve PGPand non-PGP-dependent drug efflux and provide a definitive measure of intrinsic drug permeability without recourse to inhibitors (Stephens et al., 2002). The present study uses this approach to investigate the impact of PGP on intestinal permeability of paclitaxel and digoxin in different regions of the mouse intestine (jejunum, ileum, and proximal and distal colon). Absorption of paclitaxel and digoxin in tissues from wild-type mice was low and showed little regional variation. In contrast, absorption of both drugs was markedly higher in mdr1a(Ϫ/Ϫ) intestine, although the increase was highly region-dependent, with the ileum and distal colon showing the greatest effect and much smaller changes in the jejunum and proximal colon. These effects were accompanied by the abolition of paclitaxel and digoxin secretion in mdr1a(Ϫ/Ϫ) mice, suggesting that regional variations in intestinal permeability are masked by differential PGP expression, confirmed by immunoblotting studies. Propranolol permeability, which is not influenced by PGP, showed similar regional variation in both wild-type and mdr1a(Ϫ/Ϫ) tissues, suggesting that differences are at the level of transcellular permeability. These data suggest that the ileum and the distal colon are regions of relatively high transcellular permeability for xenobiotics that are compensated by enhanced expression of PGP.

show abstract

contrasting

confidence: 50%

mentioning

confidence: 87%

mentioning

confidence: 99%

See 1 more Smart Citation

Region-Dependent Modulation of Intestinal Permeability by Drug Efflux Transporters: In Vitro Studies in mdr1a(−/−) Mouse Intestine

Stephens

Tanianis-Hughes

Higgs

et al. 2002

J Pharmacol Exp Ther

View full text Add to dashboard Cite

show abstract

“…example, Rost and colleagues (26) found that Abcc3 (MRP3) was predominantly expressed (mRNA and protein) in the ileum and colon of the rat intestine, and Chianale et al (5) found that Abcb1a (corresponding to ABCB4 in the human) mRNA, protein, and transport rate were all approximately sixfold higher in the mouse ileum vs. the duodenum. Because of the high degree of homology for ABC transporters between eukaryotes, similar findings in humans would be expected.…”

Section: Discussionmentioning

confidence: 99%

Regional variations in ABC transporter expression along the mouse intestinal tract

Mutch

Anderle²,

Fiaux

et al. 2004

Physiological Genomics

View full text Add to dashboard Cite

The ATP-binding cassette (ABC) family of proteins comprise a group of membrane transporters involved in the transport of a wide variety of compounds, such as xenobiotics, vitamins, lipids, amino acids, and carbohydrates. Determining their regional expression patterns along the intestinal tract will further characterize their transport functions in the gut. The mRNA expression levels of murine ABC transporters in the duodenum, jejunum, ileum, and colon were examined using the Affymetrix MuU74v2 GeneChip set. Eight ABC transporters (Abcb2, Abcb3, Abcb9, Abcc3, Abcc6, Abcd1, Abcg5, and Abcg8) displayed significant differential gene expression along the intestinal tract, as determined by two statistical models (a global error assessment model and a classic ANOVA, both with a P < 0.01). Concordance with semiquantitative real-time PCR was high. Analyzing the promoters of the differentially expressed ABC transporters did not identify common transcriptional motifs between family members or with other genes; however, the expression profile for Abcb9 was highly correlated with fibulin-1, and both genes share a common complex promoter model involving the NFκB, zinc binding protein factor (ZBPF), GC-box factors SP1/GC (SP1F), and early growth response factor (EGRF) transcription binding motifs. The cellular location of another of the differentially expressed ABC transporters, Abcc3, was examined by immunohistochemistry. Staining revealed that the protein is consistently expressed in the basolateral compartment of enterocytes along the anterior-posterior axis of the intestine. Furthermore, the intensity of the staining pattern is concordant with the expression profile. This agrees with previous findings in which the mRNA, protein, and transport function of Abcc3 were increased in the rat distal intestine. These data reveal regional differences in gene expression profiles along the intestinal tract and demonstrate that a complete understanding of intestinal ABC transporter function can only be achieved by examining the physiologically distinct regions of the gut.

show abstract

“…The excretion of the glutathione conjugate 2,4-dinitrophenyl-S-glutathione by Mrp2 was greatest in the jejunum, as expected by mRNA expression (Gotoh et al, 2000). The efflux transporter rat Mrp2 is higher in the proximal region (Gotoh et al, 2000;Mottino et al, 2000), whereas the Pgp efflux pump is higher distally at the jejunum and ileum (Thiebault et al, 1987;Hunter et al, 1990;Chianale et al, 1995;Lown et al, 1997b;Collett et al, 1999;Nakayama et al, 2000;Stephens et al, 2001;Li et al, 2002). The rat basolateral Mrp3 that transports drug out of the cell is higher toward the distal ileum and colon (Rost et al, 2002).…”

Section: Transporters For Absorption and Efflux At Apical Membranementioning

confidence: 99%

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

2003

View full text Add to dashboard Cite

Differences between nuclear run-off and mRNA levels for multidrug resistance gene expression in the cephalocaudal axis of the mouse intestine

Cited by 28 publications

References 35 publications

Region-Dependent Modulation of Intestinal Permeability by Drug Efflux Transporters: In Vitro Studies in mdr1a(−/−) Mouse Intestine

Region-Dependent Modulation of Intestinal Permeability by Drug Efflux Transporters: In Vitro Studies in mdr1a(−/−) Mouse Intestine

Regional variations in ABC transporter expression along the mouse intestinal tract

Modeling of Intestinal Drug Absorption: Roles of Transporters and Metabolic Enzymes (For the Gillette Review Series)

Contact Info

Product

Resources

About