Abstract
Studies were carried out to determine the actions of spironolactone (SL) and its metabolite, canrenone, on adrenal mixed function oxidases in the guinea pig. Administration of SL (25 mg/kg day for 3 days) to adult male guinea pigs decreased adrenal mitochondrial and microsomal cytochrome P-450 concentrations. The activities of various cytochrome P-450- dependent enzymes, including mitochondrial 11β-hydroxylase and microsomal 21-hydroxylase, benzo(a)-pyrene (BP) hydroxylase and ethylmorphine (EM) demethylase, were also reduced by SL treatment. Canrenone, when given at the same dose, had no effect on mitochondrial or microsomal cytochrome P-450 levels. Pretreatment with canrenone decreased 11β- and 21- hydroxylase activities but did not affect BP hydroxylation or EM demethylation. Addition of SL or canrenone to isolated adrenal mitochondria or microsomes produced typical type I difference spectra. Both compounds inhibited the binding of steroid substrates to cytochrome P-450 in isolated mitochondria and mic...
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