Brucine as a potent inducer of CYP2B3, the third member of the CYP2B subfamily P450 in rats.
We have indicated that strychnine and brucine induce concurrently an unknown P450 (2B-UP) which cross-reacts with anti-CYP2B1 antibody (Fujisaki et al., J. Pharmacol. Exp. Ther., 268, 1024-1031, 1994). We purified 2B-UP from brucine-treated rats and characterized it in this study. The purification was achieved by solubilization with sodium cholate followed by successive chromatographic steps with omega-aminooctyl-Sepharose 4B, DEAE-Sephacel and hydroxyapatite. The minimum molecular weight of purified 2B-UP was calculated to be 48000 by sodium dodecyl sulfate-gel electrophoresis. This preparation showed no Soret peak in the ultraviolet absorption spectrum indicating absence of heme. The amino terminal sequence of 2B-UP up to the 10th residue was consistent with the deduced amino acid sequence of CYP2B3 cDNA, but did not agree with the sequences of CYP2B1/2. The result strongly suggests that 2B-UP is CYP2B3. Thus, we indicated here that Strychnos alkaloid, brucine, is a potent inducer of the CYP2B3 or the closely related P450.
Yamada
H
H
Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
Minematsu
Y
Y
Nakamura
T
T
Mise
M
M
Fujisaki
H
H
Oguri
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001189:Aryl Hydrocarbon Hydroxylases; D003577:Cytochrome P-450 Enzyme System / Q000096:biosynthesis / Q000187:drug effects* / Q000302:isolation & purification; D000072467:Cytochrome P450 Family 2; D004790:Enzyme Induction / Q000187:drug effects; D008969:Molecular Sequence Data; D051381:Rats; D013331:Strychnine / Q000031:analogs & derivatives* / Q000494:pharmacology
C083806:brucine; D003577:Cytochrome P-450 Enzyme System; D001189:Aryl Hydrocarbon Hydroxylases; C089142:Cyp2b3 protein, rat; D000072467:Cytochrome P450 Family 2; D013331:Strychnine