Cytochrome P450 arachidonic acid metabolism in bovine corneal epithelium

Conference · Sat Mar 01 04:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5277800

Masferrer, J; Schwartzman, M L; Abraham, N G; Dunn, M W; McGiff, J C

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-
• Conference Information: Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Journal Volume: 45:3
• Country of Publication: United States
• Language: English

Related Subjects

550501* -- Metabolism-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ACID ANHYDRASES
ANIMAL TISSUES
ANIMALS
ARACHIDONIC ACID
ARTERIES
ATP-ASE
BLOOD VESSELS
BODY
BODY AREAS
CARBON 14 COMPOUNDS
CARBOXYLIC ACIDS
CARDIOVASCULAR SYSTEM
CATTLE
CELL CONSTITUENTS
CHROMATOGRAPHY
COENZYMES
CORNEA
CYTOCHROMES
DOMESTIC ANIMALS
DOSE-RESPONSE RELATIONSHIPS
ENZYME ACTIVITY
ENZYMES
EPITHELIUM
EYES
FACE
HEAD
HYDROLASES
ISOTOPE APPLICATIONS
LABELLED COMPOUNDS
LIQUID COLUMN CHROMATOGRAPHY
MAMMALS
METABOLISM
METABOLITES
MICROSOMES
MONOCARBOXYLIC ACIDS
NADP
NUCLEOTIDES
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANOIDS
ORGANS
PHOSPHOHYDROLASES
PIGMENTS
PROTEINS
RATS
RODENTS
RUMINANTS
SENSE ORGANS
SEPARATION PROCESSES
TISSUES
TRACER TECHNIQUES
VERTEBRATES