PMID- 11302942
OWN - NLM
STAT- MEDLINE
DCOM- 20010614
LR  - 20181130
IS  - 0090-9556 (Print)
IS  - 0090-9556 (Linking)
VI  - 29
IP  - 5
DP  - 2001 May
TI  - Effects of receptor-selective retinoids on CYP26 gene expression and metabolism 
      of all-trans-retinoic acid in intestinal cells.
PG  - 742-7
AB  - Retinoids mediate most of their function via interaction with retinoid receptors 
      [retinoic acid receptors (RARs) and retinoid X receptors (RXRs)], which act as 
      ligand-activated transcription factors controlling the expression of a number of 
      target genes. The complex mechanistic pattern of retinoid-induced effects on gene 
      expression of CYP26 and intestinal metabolism of all-trans-retinoic acid (RA) was 
      investigated here by studying the effects of retinoid ligands with relative 
      selectivity for binding and transactivation of the retinoid acid receptors, RARs 
      and RXRs, in human intestinal Caco-2 cells. We show here that CYP26 is expressed 
      in human duodenum and colon. In Caco-2 cells not only all-trans-RA but also 
      synthetic agonists of the RAR induced intestinal CYP26 gene expression and 
      all-trans-RA metabolism as well. The RARalpha ligand Am580 induced the CYP26 gene 
      expression more than the RARbeta ligand CD2019 or the RARgamma ligand CD437 
      suggesting the highest specificity for RARalpha on intestinal CYP26 gene 
      regulation. RXR ligands alone did not induce CYP26 gene expression or RA 
      metabolism in Caco-2 cells at all. But together with the RARalpha ligand, Am580, 
      there were enhanced effects on the induction of CYP26 gene expression and on the 
      induction of the metabolism of all-trans-RA. We conclude that gene regulation of 
      CYP26 and the metabolism of all-trans-RA in intestinal cells is regulated through 
      RXR and RAR heterodimerization. When coadministered, RAR agonists showed the 
      highest potency for CYP26 gene regulation. Receptor-selective retinoids showed 
      enhanced effects on induction of CYP26 gene expression and all-trans-retinoic 
      acid metabolism.
FAU - Lampen, A
AU  - Lampen A
AD  - Zentrumsabteilung fur Lebensmitteltoxikologie, Tierarztliche Hochschule Hannover, 
      Bischofsholer Damm 15, D-30173 Hannover, Germany. Alfonso.Lampen@tiho-hannover.de
FAU - Meyer, S
AU  - Meyer S
FAU - Nau, H
AU  - Nau H
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Drug Metab Dispos
JT  - Drug metabolism and disposition: the biological fate of chemicals
JID - 9421550
RN  - 0 (Receptors, Retinoic Acid)
RN  - 0 (Retinoid X Receptors)
RN  - 0 (Transcription Factors)
RN  - 5688UTC01R (Tretinoin)
RN  - 9035-51-2 (Cytochrome P-450 Enzyme System)
SB  - IM
MH  - Caco-2 Cells
MH  - Cytochrome P-450 Enzyme System/*genetics
MH  - Gene Expression Regulation, Enzymologic/*drug effects
MH  - Humans
MH  - Intestinal Mucosa/metabolism
MH  - Intestines/*drug effects/enzymology
MH  - Receptors, Retinoic Acid/*drug effects
MH  - Retinoid X Receptors
MH  - Transcription Factors/*drug effects
MH  - Tretinoin/*pharmacology
EDAT- 2001/04/17 10:00
MHDA- 2001/06/23 10:01
CRDT- 2001/04/17 10:00
PHST- 2001/04/17 10:00 [pubmed]
PHST- 2001/06/23 10:01 [medline]
PHST- 2001/04/17 10:00 [entrez]
PST - ppublish
SO  - Drug Metab Dispos. 2001 May;29(5):742-7.