Phenobarbital-Mediated Induction of the CYP2B Subfamily Is Not Antagonized by Picrotoxin, A Potent Antagonist of Barbiturates in the Central Nervous System
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概要
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Our previous study indicated that picrotoxin competes with phenobarbital (PB) for the binding to liver microsomes, although the target of biding and the physiological role were not determined (unpublished observation). To seek information on the target site of PB, reflecting the induction of hepatic enzymes, we examined here the effect of picrotoxin on PB-mediated induction of hepatic cytochrome P450 and UDP-glucuronosyltransferase in vivo in rats. The induction of the CYP2B1/2 was estimated by immunoblot analysis and by measuring the activity of testosterone 16β-hydroxylation. Intraperitoneal injection of picrotoxin alone slightly increased CYP2B1/2 protein. An experiment on co-treatment of picrotoxin and PB showed that picrotoxin enhanced rather than antagonized the inducing effect of PB. The results suggest two possibilities : that 1) picrotoxin increases the CYP2B subfamily by binding to the same site as PB; or 2) the site in microsomes for the competition between PB and picrotoxin does not reflect the induction of P450.
- 公益社団法人日本薬学会の論文
- 1998-11-15
著者
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Oguri Kazuta
Faculty Of Pharmaceutical Sciences Kyushu University
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Yamada Hideyuki
Faculty Of Pharmaceutical Sciences Kyushu University
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MATSUKI Yumie
Faculty of Pharmaceutical Sciences, Kyushu University
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Matsuki Yumie
Faculty Of Pharmaceutical Sciences Kyushu University
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