( sup 125 I)2-iodo-3,7,8-trichlorodibenzo-p-dioxin-binding species in mouse liver induced by agonists for the Ah receptor: Characterization and identification
- Univ. of Wisconsin, Madison (USA)
The admininistration of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) to C57BL/6J mice produces a dose-related increase in the hepatic uptake of ({sup 125}I)2-iodo-3,7,8-trichlorodibenzo-p-dioxin (({sup 125}I)Cl3DpD) in vivo and the binding of the radioligand to liver homogenate in vitro. The TCDD-induced hepatic binding species was found to be predominantly in the microsomal fraction and was inactivated by heating at 60 degree, trypsin, and mercurials. The TCDD-induced binding species was found to have an apparent equilibrium dissociation constant, KD, (({sup 125}I)Cl3DpD) of 56 +/- 16 nM and a pool size, Bmax, of 22 +/- 5 nmol/g of liver. A number of halogenated dibenzo-p-dioxins, biphenyls, and polycyclic aromatic hydrocarbons compete with ({sup 125}I)Cl3DpD binding to this species; all are aromatic and planar. The distinctive profile of this binding species, a protein of large pool size induced in the microsomal fraction of liver but not other tissues and induced by agonists for the Ah receptor, suggested that this moiety might be cytochrome P3-450. The coincidence of the major microsomal species covalently labeled with the photoaffinity ligand ({sup 125}I)2-iodo-3-azido-7,8-dibromodibenzo-p-dioxin and that immunochemically stained with polyclonal antiserum that binds to cytochrome P3-450 confirms this hypothesis. This is a novel role for a cytochrome P-450 isozyme, as an induced sequestration site that enhances the hepatic localization of the agonist drug.
- OSTI ID:
- 5512378
- Journal Information:
- Molecular Pharmacology; (USA), Journal Name: Molecular Pharmacology; (USA) Vol. 36:1; ISSN 0026-895X; ISSN MOPMA
- Country of Publication:
- United States
- Language:
- English
Similar Records
3-(Trifluoromethyl)-3-(m-(/sup 125/I)iodophenyl)diazirine photolabels a substrate-binding site of rat hepatic cytochrome P-450 form PB-4
Stimulation of in vivo hepatic uptake and in vitro hepatic binding of (/sup 125/I)2-lodo-3,7,8-trichlorodibenzo-p-dioxin by the administration of agonist for the Ah receptor
Related Subjects
560300* -- Chemicals Metabolism & Toxicology
59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ANIMALS
BETA DECAY RADIOISOTOPES
BIOCHEMICAL REACTION KINETICS
BODY
CHEMICAL COMPOSITION
CYTOCHROMES
DAYS LIVING RADIOISOTOPES
DIGESTIVE SYSTEM
DIOXIN
DOSE-RESPONSE RELATIONSHIPS
ELECTRON CAPTURE RADIOISOTOPES
GLANDS
HETEROCYCLIC COMPOUNDS
IN VITRO
INTERMEDIATE MASS NUCLEI
IODINE 125
IODINE ISOTOPES
ISOENZYMES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
LIGANDS
LIVER
MAMMALS
MEMBRANE PROTEINS
METABOLIC ACTIVATION
MICE
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
ORGANS
PIGMENTS
PROTEINS
RADIOISOTOPES
REACTION KINETICS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
TRACER TECHNIQUES
VERTEBRATES