Biomaterial Database

Drug induction of P450IIB1/IIB2 and 5-aminolevulinate synthase mRNAs in rat tissues. 1989

G Srivastava, and M J Bawden, and A Anderson, and B K May

Department of Biochemistry, University of Adelaide, Australia.

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.

UI	MeSH Term	Description	Entries
D007668	Kidney	Body organ that filters blood for the secretion of URINE and that regulates ion concentrations.	Kidneys
D008099	Liver	A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.	Livers
D008168	Lung	Either of the pair of organs occupying the cavity of the thorax that effect the aeration of the blood.	Lungs
D008297	Male		Males
D010634	Phenobarbital	A barbituric acid derivative that acts as a nonselective central nervous system depressant. It potentiates GAMMA-AMINOBUTYRIC ACID action on GABA-A RECEPTORS, and modulates chloride currents through receptor channels. It also inhibits glutamate induced depolarizations.	Phenemal,Phenobarbitone,Phenylbarbital,Gardenal,Hysteps,Luminal,Phenobarbital Sodium,Phenobarbital, Monosodium Salt,Phenylethylbarbituric Acid,Acid, Phenylethylbarbituric,Monosodium Salt Phenobarbital,Sodium, Phenobarbital
D011919	Rats, Inbred Strains	Genetically identical individuals developed from brother and sister matings which have been carried out for twenty or more generations or by parent x offspring matings carried out with certain restrictions. This also includes animals with a long history of closed colony breeding.	August Rats,Inbred Rat Strains,Inbred Strain of Rat,Inbred Strain of Rats,Inbred Strains of Rats,Rat, Inbred Strain,August Rat,Inbred Rat Strain,Inbred Strain Rat,Inbred Strain Rats,Inbred Strains Rat,Inbred Strains Rats,Rat Inbred Strain,Rat Inbred Strains,Rat Strain, Inbred,Rat Strains, Inbred,Rat, August,Rat, Inbred Strains,Rats Inbred Strain,Rats Inbred Strains,Rats, August,Rats, Inbred Strain,Strain Rat, Inbred,Strain Rats, Inbred,Strain, Inbred Rat,Strains, Inbred Rat
D003577	Cytochrome P-450 Enzyme System	A superfamily of hundreds of closely related HEMEPROTEINS found throughout the phylogenetic spectrum, from animals, plants, fungi, to bacteria. They include numerous complex monooxygenases (MIXED FUNCTION OXYGENASES). In animals, these P-450 enzymes serve two major functions: (1) biosynthesis of steroids, fatty acids, and bile acids; (2) metabolism of endogenous and a wide variety of exogenous substrates, such as toxins and drugs (BIOTRANSFORMATION). They are classified, according to their sequence similarities rather than functions, into CYP gene families (>40% homology) and subfamilies (>59% homology). For example, enzymes from the CYP1, CYP2, and CYP3 gene families are responsible for most drug metabolism.	Cytochrome P-450,Cytochrome P-450 Enzyme,Cytochrome P-450-Dependent Monooxygenase,P-450 Enzyme,P450 Enzyme,CYP450 Family,CYP450 Superfamily,Cytochrome P-450 Enzymes,Cytochrome P-450 Families,Cytochrome P-450 Monooxygenase,Cytochrome P-450 Oxygenase,Cytochrome P-450 Superfamily,Cytochrome P450,Cytochrome P450 Superfamily,Cytochrome p450 Families,P-450 Enzymes,P450 Enzymes,Cytochrome P 450,Cytochrome P 450 Dependent Monooxygenase,Cytochrome P 450 Enzyme,Cytochrome P 450 Enzyme System,Cytochrome P 450 Enzymes,Cytochrome P 450 Families,Cytochrome P 450 Monooxygenase,Cytochrome P 450 Oxygenase,Cytochrome P 450 Superfamily,Enzyme, Cytochrome P-450,Enzyme, P-450,Enzyme, P450,Enzymes, Cytochrome P-450,Enzymes, P-450,Enzymes, P450,Monooxygenase, Cytochrome P-450,Monooxygenase, Cytochrome P-450-Dependent,P 450 Enzyme,P 450 Enzymes,P-450 Enzyme, Cytochrome,P-450 Enzymes, Cytochrome,Superfamily, CYP450,Superfamily, Cytochrome P-450,Superfamily, Cytochrome P450
D004790	Enzyme Induction	An increase in the rate of synthesis of an enzyme due to the presence of an inducer which acts to derepress the gene responsible for enzyme synthesis.	Induction, Enzyme
D000502	Allylisopropylacetamide	An allylic compound that acts as a suicide inactivator of CYTOCHROME P450 by covalently binding to its heme moiety or surrounding protein.	2-Isopropyl-4-Pentenamide,2 Isopropyl 4 Pentenamide
D000624	5-Aminolevulinate Synthetase	An enzyme of the transferase class that catalyzes condensation of the succinyl group from succinyl coenzyme A with glycine to form delta-aminolevulinate. It is a pyridoxyal phosphate protein and the reaction occurs in mitochondria as the first step of the heme biosynthetic pathway. The enzyme is a key regulatory enzyme in heme biosynthesis. In liver feedback is inhibited by heme. EC 2.3.1.37.	Aminolevulinic Acid Synthetase,delta-Aminolevulinate Synthase,5-Aminolevulinate Synthase,delta-Aminolevulinic Acid Synthetase,5 Aminolevulinate Synthase,5 Aminolevulinate Synthetase,Acid Synthetase, Aminolevulinic,Acid Synthetase, delta-Aminolevulinic,Synthase, 5-Aminolevulinate,Synthase, delta-Aminolevulinate,Synthetase, 5-Aminolevulinate,Synthetase, Aminolevulinic Acid,Synthetase, delta-Aminolevulinic Acid,delta Aminolevulinate Synthase,delta Aminolevulinic Acid Synthetase