Bufuralol metabolism by guinea pig adrenal and hepatic microsomes.
Previous investigations demonstrated that CYP2D16 was expressed at high levels in guinea pig adrenal microsomes. The studies presented here were done to determine whether adrenal metabolism of bufuralol (BUF), a model CYP2D substrate, was similar to that in the liver. Guinea pig adrenal microsomes converted BUF to 1'-hydroxybufuralol (1'-OH-BUF) as the major metabolite and smaller amounts of a compound identified as 6-hydroxybufuralol (6-OH-BUF). In contrast, 6-OH-BUF was the major product formed by hepatic microsomal preparations. The apparent Km values were similar for 1'-OH-BUF and 6-OH-BUF production in each tissue. Quinidine, a selective CYP2D inhibitor, decreased the production of both BUF metabolites equally in liver and adrenal microsomes. Cortisol also caused equivalent decreases in the rates of 1'-OH-BUF and 6-OH-BUF formation by adrenal microsomes, but had no effect on hepatic BUF metabolism. Although both BUF metabolites may be produced by CYP2D16, unknown factors appear to effect some differences in the catalytic characteristics of BUF metabolism in adrenal and liver. The large amount of 6-OH-BUF produced distinguishes BUF metabolism in guinea pigs from that in other species previously studied.
Colby
H D
HD
Albany College of Pharmacy, Albany, NY 12208, USA. colbyh@acp-edu
Nowak
D M
DM
Longhurst
P A
PA
Zhang
X
X
Hayes
J R
JR
Voigt
J M
JM
D000311:Adrenal Glands / Q000187:drug effects / Q000378:metabolism*; D000319:Adrenergic beta-Antagonists / Q000378:metabolism; D000818:Animals; D002851:Chromatography, High Pressure Liquid; D003577:Cytochrome P-450 Enzyme System / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004983:Ethanolamines / Q000378:metabolism*; D006168:Guinea Pigs; D006854:Hydrocortisone / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D008862:Microsomes, Liver / Q000187:drug effects / Q000378:metabolism*; D011802:Quinidine / Q000494:pharmacology
D000319:Adrenergic beta-Antagonists; D004983:Ethanolamines; C010831:bufuralol; D003577:Cytochrome P-450 Enzyme System; D011802:Quinidine; D006854:Hydrocortisone