| Project/Area Number |
63480352
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| Research Category |
Grant-in-Aid for General Scientific Research (B)
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| Allocation Type | Single-year Grants |
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| Research Field |
麻酔学
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| Research Institution | Osaka City University |
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Principal Investigator |
NISHI Shin-ichi Oska City University Medical School, Research Associate, 医学部, 助手 (20189244)
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| Co-Investigator(Kenkyū-buntansha) |
ASADA Akira Osaka City University Medical School, Assistant Professor, 医学部, 助教授 (00047367)
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| Project Period (FY) |
1988 – 1990
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| Project Status |
Completed (Fiscal Year 1990)
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| Budget Amount *help |
¥5,900,000 (Direct Cost: ¥5,900,000)
Fiscal Year 1990: ¥1,600,000 (Direct Cost: ¥1,600,000)
Fiscal Year 1989: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1988: ¥2,800,000 (Direct Cost: ¥2,800,000)
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| Keywords | Lidocaine / Human liver microsome / Cytochrome P-450 / P-450_<NF> / P-450_<PA> / P-450_<MP> / ヒト肝臓Pー450 / チトクロームP-450 / HPLC / 肝臓 |
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| Research Abstract |
The metabolism of lidocaine by human heptic microsome and purified human hepatic cytochrome P-450 (P-450) isozymes, P-450_<NF> , P-450_<PA> and P-450_<MP> was studied. Microsome was prepared from normal hepatic tissue around the hepatoma cells that was obtained during hepatic surgery.Content of P-450, NADPH cytochrome P-450 reductase and cytochrome b_5 was lower than those of rat hepatic microsome, and strong interindividual variance was detected. Human hepatic microsome produced N-dealkylated metabolite, monoethylglycinexylidide (MEGX) and ring hydroxylated one (3-OH LID). There was not any relationship between the content of P-450, formation rate of these metabolites and preoperatively administered drugs like diuretics, antihypertesive drugs. By Western blotting technique, P-450_<NF> was proved to be the major isozyme of human hepatic microsome and strong correlation was detected between the content of P-450_<NF> and formation rate of MEGX, rate of nifedipine oxidation and testosterone 16B-hydroxylation. This suggests that these reactions were catalyzed by selectively P-450_<NF>. In a reconstituted system with dilauroylphosehatidylcholine. MEGX was produced by each isozyme of P-450, but most effectively by P-450_<NF> and 3-OH LID was selectively by P-450_<PA>. Formation rate of MEGX was inhibited approximately by 40% by antibody raised against P-450X_<nf> in white rabbit. These results indicates that P-450_<nf> is the major isozyme of P-450 which is involved in the metabolism of lidocaine in human liver.
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