Cytochrome P450 enzymes in the kidney of the bobwhite quail (Colinus virginianus): induction and inhibition by ergosterol biosynthesis inhibiting fungicides.
Metabolism of testosterone and the alkoxyresorufins was examined in kidney microsomes from male Bobwhite quail (Colinus virginianus) and was compared with that in kidney microsomes prepared from the male rat. In addition, cross-reactivity studies were conducted with a number of antibodies prepared against cytochrome P450 (CYP) enzymes purified from rat and trout liver. The effects of treatment with the fungicides: propiconazole, vinclozolin, clotrimazole and ketoconazole were examined. While kidney microsomes from both quail and rat catalyzed testosterone metabolism at multiple positions, the pattern of hydroxylated metabolites differed. Treatment with vinclozolin resulted in significant induction of testosterone 2 beta- and 15 beta-hydroxylase activity in quail kidney accompanied by increases in expression of P450 enzymes cross-reactive with antibodies raised against a CYP 3A-like protein in teleost fish. In contrast, ketoconazole treatment resulted in inhibition of testosterone hydroxylation at positions 15 beta- and 6 alpha-. Propiconazole and vinclozolin significantly induced a CYP 1A1 cross-reactive P450 enzyme in quail kidney 2-3-fold unaccompanied by significant increases in alkoxyresorufin O-dealkylase activity. These activities were significantly inhibited by ketoconazole treatment. Quail kidney microsomes also expressed high levels of a CYP 4A1 cross-reactive apoprotein which was inducible 3-4-fold by ketoconazole. Thus, quail kidney possesses cytochrome P450 enzymes related to forms found in mammalian gene families 1, 3 and 4. Fungicide treatment results in mixed patterns of induction and inhibition of kidney P450 enzymes different from those previously reported in quail liver.
Ronis
M J
MJ
Department of Pediatrics, University of Arkansas for Medical Sciences, Arkansas Children's Hospital Research Institute, Little Rock 72205, USA. ronismartins@exchange.uams.edu
Celander
M
M
Badger
T M
TM
D000818:Animals; D003088:Colinus / Q000378:metabolism*; D065607:Cytochrome P-450 Enzyme Inhibitors; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000378:metabolism*; D004875:Ergosterol / Q000037:antagonists & inhibitors* / Q000096:biosynthesis; D005659:Fungicides, Industrial / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D008297:Male; D008861:Microsomes / Q000187:drug effects / Q000201:enzymology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013739:Testosterone / Q000378:metabolism