Heterogeneity of rat hepatic Ah receptor: identification of two receptor forms which differ in their biochemical properties.
In cytosol, the rat hepatic Ah receptor (AhR) appears to exist in two distinct forms (AhR alpha, AhR beta) in similar concentration. The binding of ligand (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) to AhR alpha requires the receptor be in its oligomeric 8-10 to S conformation (bound to other protein subunits), while ligand binding to AhR beta can occur with the dissociated 5-6 S form. Occupancy of AhR alpha by ligand (TCDD) protects it from salt-dependent inactivation; AhR beta is not inactivated by high salt conditions. The addition of molybdate to cytosol during tissue homogenization stabilized AhR alpha against salt-dependent inactivation and subunit dissociation but did not prevent dissociation of AhR beta by high salt. Although the presence of molybdate appears to stabilize AhR alpha in its oligomeric 8-10 S, it had no significant effect on the overall amount of TCDD:AhR complex which bound to its specific DNA recognition site, the dioxin responsive element (DRE). These results suggest that AhR alpha, unlike AhR beta, is either unable to transform or bind to the DRE with high affinity.
Denison
M S
MS
Department of Biochemistry, Michigan State University, East Lansing 48824.
D000818:Animals; D001483:Base Sequence; D003600:Cytosol / Q000737:chemistry; D004247:DNA / Q000378:metabolism; D066298:In Vitro Techniques; D008099:Liver / Q000737:chemistry*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D008982:Molybdenum / Q000494:pharmacology; D009994:Osmolar Concentration; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000032:analysis* / Q000187:drug effects / Q000378:metabolism
D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; C044659:molybdate; D011189:Potassium Chloride; D008982:Molybdenum; D004247:DNA