Intracellular location of the Ah receptor.
The subcellular distribution of the Ah receptor from the mouse hepatoma line, Hepa-1, was investigated following cytochalasin B treatment and cell enucleation. Probing the resultant cytoplast and nucleoplast fractions with radiolabelled tetrachlorodibenzo-p-dioxin (TCDD) revealed the presence of a specifically bound peak of receptor only in the cytoplast fraction. However, the quantity of receptor recovered in these experiments was only 10-12% of the expected value. We therefore undertook an investigation to determine the fate of the Ah receptor in the presence of cytochalasin B. Incubation of Hepa-1 cells with this compound resulted in a rapid loss or inactivation of cytosolic binding activity with a concomitant decrease in the amount of receptor partitioned into the nucleus at all time periods examined. Control experiments indicated that cytochalasin B did not compete with TCDD for binding to the Ah receptor and furthermore, that its mechanism of action could not be attributed to a non-specific effect on all cytosolic proteins. The results obtained are discussed in relation to the proposed models for induction by the estrogen and glucocorticoid binding receptors.
D000818:Animals; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D003571:Cytochalasin B / Q000494:pharmacology; D003600:Cytosol / Q000032:analysis*; D004147:Dioxins / Q000378:metabolism*; D005954:Glucosephosphate Dehydrogenase / Q000032:analysis; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000032:analysis* / Q000648:ultrastructure; D051379:Mice; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000032:analysis*
D004147:Dioxins; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D003571:Cytochalasin B; D003513:Cycloheximide; D005954:Glucosephosphate Dehydrogenase