Inhibition of adrenocortical, mitochondrial and microsomal monooxygenases by SU-10'603, a steroid 17 alpha-hydroxylase inhibitor.
SU-10'603 is a pyridine derivative that is widely used as a steroid 17 alpha-hydroxylase inhibitor. Studies were done to evaluate its effects in vitro on several other monooxygenases in guinea pig adrenal mitochondrial and microsomal preparations. In adrenal mitochondria, SU-10'603 produced a concentration-dependent inhibition of 11 beta-hydroxylation; 50% inhibition was obtained at a concentration of approximately 0.5 mM. Its potency was similar to that of the 11 beta-hydroxylase inhibitor, metyrapone. SU-10'603 was a more potent inhibitor of cholesterol sidechain cleavage (CSC) than of 11 beta-hydroxylation; a 50% decline in CSC activity was produced by an inhibitor concentration of approximately 0.1 mM. In adrenal microsomal preparations, SU-10'603 had no effect on the rate of 21-hydroxylation of 17 alpha-hydroxyprogesterone. However, SU-10'603 was a potent inhibitor of adrenal microsomal xenobiotic metabolizing monooxygenases (benzo[a]pyrene hydroxylase, benzphetamine demethylase), effecting approximately 50% inhibition of both reactions at a concentration of 0.05 mM. The results indicate that SU-10'603 inhibits several monooxygenases in the guinea pig adrenal cortex and is thus not specific for 17 alpha-hydroxylation.
LaCagnin
L B
LB
Department of Pharmacology and Toxicology, Philadelphia College of Pharmacy and Science, PA 19104.
Levitt
M
M
Bergstrom
J M
JM
Colby
H D
HD
D000302:Adrenal Cortex / Q000187:drug effects* / Q000201:enzymology; D000818:Animals; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D008861:Microsomes / Q000187:drug effects* / Q000201:enzymology; D008928:Mitochondria / Q000187:drug effects* / Q000201:enzymology; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors; D009281:Naphthalenes / Q000494:pharmacology*; D010105:Oxygenases / Q000037:antagonists & inhibitors*; D013764:Tetrahydronaphthalenes / Q000494:pharmacology*
D009281:Naphthalenes; D013764:Tetrahydronaphthalenes; C001953:SU 10603; D006899:Mixed Function Oxygenases; D010105:Oxygenases