| pubmed-article:3800382 | pubmed:abstractText | Polycyclic aromatic hydrocarbons bind to a cytosolic receptor that translocates into the nucleus and induces the synthesis of mRNA for a subset of cytochrome P-450 isozymes. The failure to detect a "phenobarbital" receptor, however, suggests that the induction of P-450b/e, the isozymes induced by phenobarbital, is mediated by a less direct mechanism. One attractive alternative is that a receptor exists for an endogenous substance that is specifically turned over by the trace amounts of P-450b/e present in uninduced liver. Changes in the concentration of this substance caused by agents that inhibit P-450b/e would then trigger the induction response. We report here that suppressing the catalytic activities of P-450b/e for prolonged periods with 1-aminobenzotriazole, a mechanism-based irreversible inhibitor, neither induces P-450b/e nor interferes with induction of these isozymes at the level of transcription by phenobarbital. The results argue against mechanisms for the induction of P-450b/e keyed to the effective catalytic availability of these isozymes. | lld:pubmed |
