Characterization of a Phenobarbital-Inducible Ah Receptor-like Protein in the Sprague-Dawley Rat

Immature male Sprague-Dawley rats were treated with phenobarbital (PB) at a dose of 50 mg/kg for 3 successive days and then sacrificed 1, 6, or 9 days after the last treatment. An increase in the concentration of hepatic cytosolic proteins able to bind specifically to [3H]- 2,3,7,8-tetrachlorodibenzo-p-dioxin ([3H]TCDD) was observed. The level of the induced protein fell in parallel with the elimination of PB in vivo. Readministration of PB 9 days after the last treatment, by which time only the constitutive receptor was present, induced additional protein at levels similar to those obtained upon the original administration of the drug. There was considerable variability within a given treatment group in both the ratio of constitutive to induced protein and the total amounts of these proteins. The kinetic properties of the induced protein were significantly different from those of the constitutive Ah receptor. In particular, [3H]TCDD was released faster from the liganded induced protein than from the constitutive Ah receptor. The protein induced by PB had properties very similar to those of the protein induced by a combination of 2,3,7,8-tetrachlorodibenzo-p-dioxin and 2,2′,4,4′,5,5′-hexachlorobiphenyl.