The hepatic Ah receptor for 2,3,7,8-tetrachlorodibenzo-p-dioxin: species differences in subunit dissociation.
2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD, dioxin) produces many of its biological effects by binding to a soluble, intracellular protein (the Ah receptor (AhR]. The hepatic AhR, from a variety of species, is present in low salt cytosol as a form which sediments at 8-10 S. High salt (0.4 M KCL) dissociates the rat, guinea pig, and rabbit cytosolic TCDD:AhR complex to a form which sediments at 5-6 S. In contrast, high salt conditions failed to dissociate the 8-10 S TCDD:AhR complex present in any of the mouse strains studied. Incubation of cytosol with heparin resulted in a shift of the [3H]TCDD:AhR complex to a smaller sedimenting form in all species. Mouse TCDD:AhR complex sedimented at 8-10 S when cytosol was simultaneously incubated with high salt and heparin, indicating that the interaction of heparin with the AhR was electrostatic in nature. Incubation of heparin-dissociated mouse TCDD:AhR complex (5-6 S) with high salt resulted in reassociation of AhR to a form which sediments at 8-10 S. Our data suggests that the resistance of mouse AhR to salt-mediated dissociation may be due to a property of the receptor protein itself and also indicates that mouse hepatic cytosolic AhR is distinctly different from that present in all other species examined to date.
Denison
M S
MS
Department of Biochemistry, Michigan State University, East Lansing 48824.
Vella
L M
LM
D000818:Animals; D002499:Centrifugation, Density Gradient; D003600:Cytosol / Q000378:metabolism; D004147:Dioxins / Q000378:metabolism*; D006168:Guinea Pigs; D006493:Heparin / Q000494:pharmacology; D008099:Liver / Q000378:metabolism*; D046911:Macromolecular Substances; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D000072317:Polychlorinated Dibenzodioxins / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug / Q000302:isolation & purification / Q000378:metabolism*; D013045:Species Specificity
D004147:Dioxins; D046911:Macromolecular Substances; D000072317:Polychlorinated Dibenzodioxins; D018336:Receptors, Aryl Hydrocarbon; D011955:Receptors, Drug; D006493:Heparin