title: Reversible inactivation of the Ah receptor associated with changes in intracellular ATP levels.
abstract: We have previously demonstrated that incubation of Hepa-1 cells in the presence of cytochalasin B (CB) results in a time- and temperature-dependent loss of 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) binding activity (Gudas et al., 1986). We show here that this loss of binding activity is probably attributable to a CB induced inhibition of glucose transport, as incubation of cells in the presence of glycolytic inhibitors or in glucose free medium caused a similar effect. All conditions leading to loss of binding also caused a marked reduction in cellular ATP concentration, suggesting that ATP (or perhaps another energy-dependent molecule) is required for maintaining the receptor in the active state. Inactivation of the Ah receptor occurred in the cytosol but not when it had translocated to the nucleus. Reactivation of receptor binding activity occurred readily in vivo and did not require de novo protein synthesis. However, attempts to restore receptor binding activity in vitro were not successful. To our knowledge this is the first reported evidence indicating that the TCDD binding Ah receptor can exist in both an inactive and an active form, with the amount present in the active ligand binding form being coupled to the energy state of the cells.
mesh_terms: D000255:Adenosine Triphosphate / Q000378:metabolism*; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D004147:Dioxins / Q000378:metabolism*; D008114:Liver Neoplasms, Experimental / Q000378:metabolism*; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000378:metabolism*
chemical_list: D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D000255:Adenosine Triphosphate