Characterization of the oxidation reactions catalyzed by CYP2D enzyme in rat renal microsomes.
Monooxygenase activities in rat renal microsomes were determined with the substrates of hepatic CYP2D enzymes. Seven kinds of CYP2D-mediated monooxygenase activities and immunochemically determined CYP2D contents in kidneys corresponded to approximately 3% of those in livers. Debrisoquine 4-hydroxylase and bunitrolol 4-hydroxylase in renal microsomes were inhibited almost completely by the antibody against a CYP2D enzyme purified from rat liver. A marked strain difference (Wistar > Dark Agouti) in these activities was observed in kidney like in liver. The two hydroxylases were inhibited stereoselectively by quinine and quinidine both in renal and hepatic microsomes. Substrate stereoselectivity in (+)- and (-)-bunitrolol 4-hydroxylase activities in kidneys was also consistent with that in livers. These results suggested that the CYP2D enzyme(s) was expressed in the kidney at levels much less than in the liver but had similar functions to those in the liver.
Masubuchi
Y
Y
Laboratory of Biopharmaceutics, Faculty of Pharmaceutical Sciences, Chiba University, Japan.
Yamamoto
K
K
Suzuki
T
T
Horie
T
T
Narimatsu
S
S
D000818:Animals; D019389:Cytochrome P-450 CYP2D6; D003577:Cytochrome P-450 Enzyme System / Q000172:deficiency / Q000502:physiology*; D003647:Debrisoquin / Q000378:metabolism; D005260:Female; D007668:Kidney / Q000378:metabolism*; D008297:Male; D008861:Microsomes / Q000378:metabolism*; D006899:Mixed Function Oxygenases / Q000172:deficiency; D010084:Oxidation-Reduction; D011412:Propanolamines / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013379:Substrate Specificity
D011412:Propanolamines; D003577:Cytochrome P-450 Enzyme System; D006899:Mixed Function Oxygenases; D019389:Cytochrome P-450 CYP2D6; C084811:bunitrolol; D003647:Debrisoquin