Inorganic tin -- a new selective inducer of the murine coumarin 7-hydroxylase (CYP2A5).
The coumarin 7-hydroxylase of mice (Coh, CYP2A5) is known to be highly selectively inducible by both a set of heavy metals such as cobalt, indium and cerium and a variety of organic nitrogen-containing heteroaromatic compounds such as 3-amino-1,2,4-triazole, pyrazine and pyrazole. The investigations presented reveal that inorganic divalent tin has to be included in the list of selective inducers. Pretreatment of NMRI-mice with 50 mg SnCl2/kg body weight, daily for 2 days, increases the coumarin hydroxylation 40- and 20-fold in the kidney and liver, respectively. So far, the inducing potency of tin chloride is higher than that of the agents already known. The diagnostic inhibitor metyrapone strongly inhibits the coumarin model reaction. In the kidneys tin generates an almost pure fraction of a cytochrome P450 isozyme catalyzing the metabolism of coumarins, as inhibition experiments reveal.
Emde
B
B
Department of Pharmacology and Toxicology, Philipps-University, Marburg, Germany.
Tegtmeier
M
M
Hahnemann
B
B
Legrum
W
W
D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D065637:Cytochrome P-450 CYP2A6; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis*; D000072467:Cytochrome P450 Family 2; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction; D007668:Kidney / Q000187:drug effects / Q000201:enzymology; D008297:Male; D008797:Metyrapone / Q000494:pharmacology; D051379:Mice; D008861:Microsomes / Q000187:drug effects / Q000378:metabolism; D006899:Mixed Function Oxygenases / Q000037:antagonists & inhibitors / Q000096:biosynthesis*; D017971:Tin Compounds / Q000633:toxicity*
D065607:Cytochrome P-450 Enzyme Inhibitors; D017971:Tin Compounds; C023599:stannous chloride; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D001189:Aryl Hydrocarbon Hydroxylases; C585520:Cyp2a5 protein, mouse; D065637:Cytochrome P-450 CYP2A6; D000072467:Cytochrome P450 Family 2; D008797:Metyrapone