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 (AhRα, AhRβ) in similar concentration. The binding of ligand (2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD)) to AhRα requires the receptor be in its oligomeric 8–10 to S conformation (bound to other protein subunits), while ligand binding to AhRβ can occur with the dissociated 5–6 S form. Occupancy of AhRβ by ligand (TCDD) protects it from salt-dependent inactivation; AhRβ is not inactivated by high salt conditions. The addition of molybdate to cytosol during tissue homogenization stabilized AhRα against salt-dependent inactivation and subunit dissociation but did not prevent dissociation of AhRβ by high salt. Although the presence of molybdate appears to stabilize AhRα 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 AhRα, unlike AhRβ, is either unable to transform or bind to the DRE with high affinity.