Effect of drugs and hormones on rat liver dimethylaminoazobenzene reductase activity.
1. Rat liver endoplasmic reticulum catalyzes the reduction of 4-dimethylaminoazobenzene (DAB) by NADPH to dimethyl-p-phenylenediamine and p-aminophenol. This azoreductase activity was inhibited by cyanide and cytochrome b5 antibody, but was resistant to carbon monoxide and SKF-525A (beta-diethylaminoethyl-diphenylpropylacetate). 2. DAB azoreductase activity was induced by 20-methylcholanthrene and phenobarbital, and increased in streptozotocin-induced diabetes or fasting. It was repressed by treatment with DAB and its 3'-methyl derivative, but not by several other derivatives with substitutions in the dimethylaminoazobenzene ring. 3. Azoreductase activity, NADPH-cytochrome P-450 reductase, cytochromes P-450 and b5 were measured in liver microsomes prepared from fasted animals and from animals treated with 20-methylcholanthrene, phenobarbital, streptozotocin or 3-aminotriazole plus allyl-isopropylacetamide. No direct correlation could be established between the variations of azoreductase activity and those of cytochromes P-450 and b5, and of NADPH-cytochrome P-450 reductase in these experimental situations. Since these known carriers do not seem to be the limiting factors for the azoreductase activity, the participation of an unknown carrier that can be repressed by dimethylaminoazobenzene is postulated. 4. Dimethylaminoazobenzene treatment did not reduce the rate of synthesis of microsomal proteins but rather increased the turnover rate of proteins with molecular weights of about 17, 30 an 35 kdal. Since streptozotocin increased the synthesis of proteins with molecular weights of 17, 32, and 48 kdal it is suggested that one of these proteins may correspond to the postulated carrier that is the limiting factor in DAB reduction.
D000502:Allylisopropylacetamide / Q000494:pharmacology; D000640:Amitrole / Q000494:pharmacology; D000818:Animals; D003577:Cytochrome P-450 Enzyme System / Q000378:metabolism; D005260:Female; D066298:In Vitro Techniques; D008748:Methylcholanthrene / Q000494:pharmacology*; D008862:Microsomes, Liver / Q000187:drug effects* / Q000201:enzymology; D009247:NADH, NADPH Oxidoreductases / Q000378:metabolism*; D010634:Phenobarbital / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D013311:Streptozocin / Q000494:pharmacology*; D013974:Thyroxine / Q000494:pharmacology; D004124:p-Dimethylaminoazobenzene / Q000378:metabolism*
D000502:Allylisopropylacetamide; D008748:Methylcholanthrene; D013311:Streptozocin; D003577:Cytochrome P-450 Enzyme System; D004124:p-Dimethylaminoazobenzene; D009247:NADH, NADPH Oxidoreductases; D013974:Thyroxine; D010634:Phenobarbital; D000640:Amitrole