Selective inhibition by chloramphenicol of pregnenolone-16. cap alpha. -carbonitrile-inducible rat liver cytochrome P-450 isozymes

Conference · Fri Feb 28 23:00:00 EST 1986 · Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States)

OSTI ID:5393482

Graves, P E; Kaminsky, L S; Halpert, J

Pregnenolone-16 ..cap alpha..-carbonitrile (PCN) has been shown to induce, in male rats, cytochrome P-450 isozymes responsible for the formation of R-10-hydroxywarfarin and R-dehydrowarfarin. Antibodies to the major PCN-inducible isozyme (PB/PCN-E) inhibit both activities in microsomal preparations. Recently the authors have shown that PCN treatment of female rats also induces the formation of both R-warfarin metabolites. However, in both sexes chloramphenicol (CAP) treatment selectively inhibits only the rate of formation of the R-dehydrowarfarin. A decrease in microsomal P-450 content occurs after in vivo administration of CAP to PCN-treated rats of both sexes. This is in contrast to the lack of effect of CAP on P-450 levels in phenobarbital-treated rats. Covalent binding of /sup 14/C-CAP to microsomal protein in vitro was increased 3 to 4-fold following PCN treatment. Chromatographic evidences suggests the presence of at least two PCN-induced isozymes of similar molecular weights in both male and female rat liver microsomes. These data are consistent with the multiplicity of PCN-inducible P-450 in rat liver.

• Research Organization: Univ. of Arizona, Tucson
• OSTI ID: 5393482
• Report Number(s): CONF-8604222-
• Journal Information: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States), Journal Name: Fed. Proc., Fed. Am. Soc. Exp. Biol.; (United States) Vol. 45:3; ISSN FEPRA
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ANIMALS
ANTI-INFECTIVE AGENTS
ANTIBIOTICS
BIOCHEMICAL REACTION KINETICS
BIOLOGICAL EFFECTS
BODY
CARBON 14 COMPOUNDS
CHLORAMPHENICOL
CHROMATOGRAPHY
COVALENCE
CYTOCHROMES
DIGESTIVE SYSTEM
DRUGS
ENZYME ACTIVITY
GLANDS
HYDROXY COMPOUNDS
HYDROXYPREGNENONE
KETONES
KINETICS
LABELLED COMPOUNDS
LIVER
MAMMALS
MOLECULAR WEIGHT
ORGANIC COMPOUNDS
ORGANS
PIGMENTS
PREGNANES
PROTEINS
RATS
REACTION KINETICS
RODENTS
SEPARATION PROCESSES
STEROIDS
VERTEBRATES