title: Retinoic acid metabolism in cultured retinal pigment epithelial cells.
abstract: OBJECTIVE
  To examine the stability of retinoic acid administered to cultured bovine retinal pigment epithelial (RPE) cells and to determine if RPE cells metabolize retinoic acid by a cytochrome P-450 mechanism.
  
  
  METHODS
  Retinoic acid metabolism was examined in cultured RPE cells and subcellular fractions quantitatively by a thin-layer chromatography procedure and qualitatively by normal and reverse phase high-performance liquid chromatography.
  
  
  RESULTS
  Cultured bovine RPE cells were found to have an activity that converts retinoic acid into more polar metabolites rapidly released from the cell. The highest specific activity for this process is found in the post-mitochondrial pellet (100,000g), is induced by retinoic acid, and is inhibited by ketoconazole. The major product of the RPE cell-mediated metabolism of retinoic acid is 4-oxo-retinoic acid, a known P-450 monooxygenase product of retinoic acid. The retinoic acid metabolizing activity is greatest in primary RPE cultures and decreases with aging in culture.
  
  
  CONCLUSIONS
  These data suggest that a cytochrome P-450 monooxygenase is involved in the metabolism of retinoic acid in RPE cells, and this is similar to the findings of other investigators using other cells and tissues. The authors' findings suggest that the RPE may be important in the deactivation of this biologically potent retinoid in the retina.
authors.affiliation: Schepens Eye Research Institute, Boston, Massachusetts.
authors.forename: J W
authors.initials: JW
authors.lastname: Doyle
authors.forename: R K
authors.initials: RK
authors.lastname: Dowgiert
authors.forename: S M
authors.initials: SM
authors.lastname: Buzney
mesh_terms: D000818:Animals; D002417:Cattle; D002455:Cell Division; D002478:Cells, Cultured; D002855:Chromatography, Thin Layer; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D007654:Ketoconazole / Q000494:pharmacology; D010105:Oxygenases / Q000378:metabolism; D010857:Pigment Epithelium of Eye / Q000187:drug effects / Q000378:metabolism*; D013347:Subcellular Fractions / Q000378:metabolism; D014212:Tretinoin / Q000378:metabolism*
chemical_list: D014212:Tretinoin; D003577:Cytochrome P-450 Enzyme System; D010105:Oxygenases; D007654:Ketoconazole