Acute effect of amitriptyline, phenobarbital or cobaltous chloride on .DELTA.-aminolevulinic acid synthetase, heme oxygenase and microsomal heme content and drug metabolism in rat liver.
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概要
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Cobaltous chloride (CoCl<SUB>2</SUB>) caused very marked decreases of cytochrome P-450, <I>b</I><SUB>5</SUB> and total heme contents and an increase of heme oxygenase activity. On the contrary, phenobarbital (PB) increased hepatic drug-metabolizing enzymes, but the total heme content remained unchanged. On the other hand, amitriptyline (AMT) caused a marked increase of δ-aminolevulinic acid (δ-ALA) synthetase activity at 12 and 24 hr. In addition, the contents of total heme and cytochrome <I>b</I><SUB>5</SUB> and the activities of aminopyrine (AM) N-demethylase and aniline (AN) hydroxylase at 24 hr were also increased by AMT, whereas cytochrome P-450 content did not change. This may be explained by the fact that AMT would increase hepatic heme synthesis through the prolonged induction of δ-ALA synthetase, but it may not cause an increase in cytochrome P-450 heme because there are increases in the contents of cytochrome <I>b</I><SUB>5</SUB> and total heme.
著者
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Hoshi Katsuji
Department Of Clinical Pharmacology Hokkaido College Of Pharmacy
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Fujino Sumiko
Department Of Pharmacology Hokkaido Institute Of Pharmaceutical Sciences:department Of Pharmacology
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SENDA Naoto
Department of Pharmacology, Hokkaido Institute of Pharmaceutical Sciences
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