Drug induction of P450IIB1/IIB2 and 5-aminolevulinate synthase mRNAs in rat tissues

Abstract

Expression of the phenobarbitone-inducible cytochrome P-450 mRNA species (cytochrome P450IIB1/IIB2) has been investigated in tissues of rats following administration of 2-allyl-2-isopropylacetamide or phenobarbitone. Using a cDNA probe complementary to these mRNAs, a 2.1 kb mRNA species was detected in liver and lung of untreated rats and to a lesser extent in kidney. This species was not detected in testis, brain or erythroid spleen. Following drug treatment, this mRNA species was increased in liver and kidney, particularly after administration of 2-allyl-2-isopropylacetamide. Using oligomeric probes specific for cytochrome P-450 IIB1/IIB2 mRNAs it was shown that both mRNAs are present in untreated liver and are induced by drug treatment, while in lung only cytochrome P-450 IIB1 was detected and this was not induced. However, in kidney, neither of these mRNAs could be detected, even after drug treatment. This indicates that either the levels of these mRNAs in kidney are below the limit of detection or that a related mRNA is induced which does not hybridize to the oligomeric probes. This represents the first report of a phenobarbitone-inducible cytochrome P-450 mRNA in rat kidney. The tissue-specific drug induction of cytochrome P-450 mRNAs correlated with an increased level of mRNA for 5-aminolevulinate synthase. This finding is compatible with the proposal that induction of 5-aminolevulinate synthase is dependent upon the lowering of heme levels through increased amounts of cytochrome P-450 apoprotein.