Cytochrome P450 arachidonic acid metabolism in bovine corneal epithelium
The presence of the cytochrom P450 system and its involvement in the metabolism of AA was studied in the corneal epithelium. This tissue contains cytochrome P450 as assessed directly by measurement of the carbon monoxide reduced spectrum (specific activity of 161 pmol/10 mg protein) and indirectly by measuring the activity of aryl hydrocarbon hydroxylase (AHH) - a cytochrome P450-dependent enzyme (11-39 pmol 3-OH benzopyrene/mg protein/10 min). When corneal epithelial microsomes were incubated with /sup 14/C-arachidonic acid, 30-50% of the total radioactivity was converted to two peaks, I and II. Further separation using high performance liquid chromatography has shown that each peak contains two metabolites, A,B and C,D. Metabolite formation was dependent on the addition of NADPH (1 mM) and inhibited by carbon monoxide and SKF-525A (100 ..mu..M) suggesting a cytochrome P450-dependent mechanism. Compound C (5-10 ..mu..M) inhibited the activity of corneal epithelial Na-K-ATPase by 30-60%, being 100-fold more potent than ouabain. Compound D (10-100 ng) induced a dose dependent relaxation of the rat caudal artery. Compound D also inhibited corneal Na-K-ATPase activity but less potently than compound C. These compounds may be important to transport processes of ocular epithelia and participate in the control of the ocular circulation and aqueous humor dynamics.
- Research Organization:
- New York Medical College, Valhalla
- OSTI ID:
- 5277800
- Report Number(s):
- CONF-8604222-; TRN: 86-030486
- Journal Information:
- Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Vol. 45:3; Conference: 70. annual meeting of the Federation of American Society for Experimental Biology, St. Louis, MO, USA, 13 Apr 1986
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
ARACHIDONIC ACID
METABOLISM
CORNEA
ARTERIES
ATP-ASE
CARBON 14 COMPOUNDS
CATTLE
CYTOCHROMES
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
EPITHELIUM
LIQUID COLUMN CHROMATOGRAPHY
METABOLITES
MICROSOMES
NADP
RATS
TRACER TECHNIQUES
ACID ANHYDRASES
ANIMAL TISSUES
ANIMALS
BLOOD VESSELS
BODY
BODY AREAS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CHROMATOGRAPHY
COENZYMES
DOMESTIC ANIMALS
ENZYMES
EYES
FACE
HEAD
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
MAMMALS
MONOCARBOXYLIC ACIDS
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PHOSPHOHYDROLASES
PIGMENTS
PROTEINS
RODENTS
RUMINANTS
SENSE ORGANS
SEPARATION PROCESSES
TISSUES
VERTEBRATES
550501* - Metabolism- Tracer Techniques