Brucine as a Potent Inducer of CYP2B3,the Third Member of the CYP2B Subfamily P450 in Rats

概要

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We have indicated that strychnine and brucine induce concurrently an unknown P450 (2B-UP) which crossreacts 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 ω-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.
公益社団法人日本薬学会の論文
1996-02-15