Site-Selective Oxidation of Strychnine by Phenobarbital Inducible Cytochrome P-450
スポンサーリンク
概要
- 論文の詳細を見る
The metabolism of strychnine was studied using liver microsomes of rats treated with phenobarbital or 3-methylcholanthrene (MC). The phenobarbital-treatment resulted in 7.9-fold and 4.8-fold increases in 2-hydroxylation and N-oxidation of strychnine, respectively. The formation of 16-hydroxystrychnine, strychnine 21,22-epoxide and 22-hydroxystrychnine was induced about 2-fold. MC-treatment resulted in only 1.4-fold induction of each oxidation activity. In addition, strychnine 2-hydroxylation activity was markedly induced in liver microsomes of phenobarbital-treated mice, guinea pigs, rabbits and dogs (2.5-10.5-fold). Induction of N-oxidation activity was also higher than that of the three other oxidation activities. A reconstituted system of strychnine metabolism using cytochrome P-450 isozymes, P-450I (P450IIB1) and P-450II (P450IIB2), purified from liver microsomes of phenobarbital-treated rats showed significantly high and selective activities towards 2-hydroxylation and N-oxidation of strychnine. This characteristic metabolism of strychnine appears to occur in common with interspecies P450IIB gene subfamily. The pH Optima of 2-hydroxylation and N-oxidation of strychnine were between 8.4 and 8.6 in the microsomes of phenobarbital-treated rats, while that of N-demethylation of benzphetamine, a typical substrate of phenobarbital-inducible cytochrome P-450,was between 7.4 and 7.6. In a reconstituted system with P-450I, strychnine oxidation was little affected by pH change, while benzphetamine N-demethylation activity was decreased in the alkaline side. Among several oxidations tested, only ethylmorphine N-demethylation underwent the same pH effect as did strychnine oxidation with the microsomes and reconstituted system. These results indicate that the optimum conditions for a P-450 isozyme to interact with the substrates may not necessarily be the same.
- 社団法人日本薬学会の論文
著者
-
Tanimoto Yoko
Faculty Of Pharmaceutical Sciences Kyushu University
-
YOSHIMURA HIDETOSHI
Faculty of Pharmaceutical Sciences, Kyushu University
-
Oguri K
School Of Pharmaceutical Sciences Kyushu University Of Health And Welfare
-
KANEKO Hayato
Faculty of Pharmaceutical Sciences, Kyushu University
-
OHKUMA Toyomi
Faculty of Pharmaceutical Sciences, Kyushu University
-
OGURI Kazuta
Faculty of Pharmaceutical Sciences, Kyushu University
-
Yoshimura Hidetoshi
Faculty Of Pharmaceutical Sciences Kyushu University
-
Oguri Kazuta
Faculty Of Pharmaceutical Sciences Kyushu University
-
Oguri K
Faculty Of Pharmaceutical Sciences Kyushu University
-
Oguri K
Kyushu Univ. Fukuoka Jpn
-
Kaneko Hayato
Faculty Of Pharmaceutical Sciences Kyushu University
-
Ohkuma Toyomi
Faculty Of Pharmaceutical Sciences Kyushu University
-
Yamada H
Graduate School Of Pharmaceutical Sciences Kyushu University
-
Yoshimura Hidetoshi
Department Of Food And Nutrition Nakamura Gakuen
-
Oguri Kazuta
Faculty Of Pharmaceutical Sciences Kyushu University:(present Address)laboratory Of Safety Assessment Panapharm Laboratories Co. Ltd.:(present Address)department Of Food And Nutrition Nakamura Gakuen College
関連論文
- FURTHER STUDIES ON SULFOXIDE-REDUCING ENZYME SYSTEM
- STUDIES ON ENZYMIC REDUCTION OF NITRO COMPOUNDS
- COMPOSITION AND PROPERTIES OF SULFOXIDE-REDUCING ENZYME SYSTEMS
- SULFOXIDE-REDUCING ENZYME SYSTEMS
- METABOLISM IN VITRO OF SULINDAC. SULFOXIDE-REDUCING ENZYME SYSTEMS IN GUINEA PIG LIVER
- STUDIES ON METABOLIC ACTIVATION OF NITROFURANS : FORMATION OF ACTIVE METABOLITES AND THEIR BINDING TO CYSTEINE AND GLUTATHIONE
- RELATIONSHIP BETWEEN BIOLOGICAL ACTIVITIES AND ENZYMATIC REDUCTION OF NITROFURAN DERIVATIVES
- Modulation of UDP-Glucuronosyltransferase 2B7 Function by Cytochrome P450s in Vitro : Differential Effects of CYP1A2, CYP2C9 and CYP3A4(Communications to the Editor)
- Site-Selective Oxidation of Strychnine by Phenobarbital Inducible Cytochrome P-450
- SITE-SELECTIVE OXIDATION OF STRYCHNINE BY PHENOBARBITAL INDUCIBLE CYTOCHROME P-450
- Species Difference in Metabolism of Strychnine with Liver Microsomes of Mice, Rats, Guinea Pigs, Rabbits and Dogs
- METABOLIC FATE OF STRYCHNINE IN VITRO
- MECHANISM OF SLEEP-PROLONGATING EFFECT OF Δ^8-TETRAHYDROCANNABINOL (Δ^8-THC) AND ITS METABOLITES
- IDENTIFICATION AND DETERMINATION OF 11-OXO-Δ^8-TETRAHYDROCANNABINOL AS AN INTERMEDIATE METABOLITE OF Δ^8-TETRAHYDROCANNABINOL IN THE MOUSE BRAIN AND LIVER
- UDP-GLUCURONYLTRANSFERASE ACTIVITIES OF RABBIT LIVER MICROSOMES FOR CANNABINOIDS
- METABOLIC CONVERSION OF Δ^8-TETRAHYDROCANNABINOL (Δ^8-THC) TO Δ^8-THC-11-OIC ACID AND ITS PHARMACOLOGICAL IMPLICATIONS
- METABOLISM OF 11-HYDROXY-Δ^8-THC TO 11-OXO-Δ^8THC IN RATS (The Fourth Meeting for the Study of Toxic Effect)
- Inhibitory Effect of Cannabidiol Hydroxy-quinone, and Oxidative Product of Cannabidiol, on the Hepatic Microsomal Drug-Metabolizing Enzymes of Mice
- INTERACTION OF CANNABINOIDS WITH HEPATIC MICROSOMAL DRUG-METABOLIZING ENZYME SYSTEM IN THE RAT
- EFFECTS OF TWO CANNABINOIDS ON HEPATIC MICROSOMAL CYTOCHROME P-450
- METABOLIC ACTIVATION OF Δ^8-THTRAHYDROCANNABINOL (Δ^8-THC) AT THE 7-POSITION AND MECHANISM OF THE OXIDATION OF 7-HYDROXY-Δ^8-THC TO 7-OXO-Δ^8-THC WITH LIVER MICROSOMES
- IN VITRO METABOLISM OF TETRAHYDROCANNABINOL (THC) BY HUMAN LIVER MICROSOMES. EPOXIDE-DIOL PATHWAY OF THC
- THE PROPERTIES OF UDP-GLUCURONYLTRANSFERASE FOR CANNABINOIDS IN RAT LIVER MICROSOMES
- TOXICOLOGICAL ASSESSMENT OF POLYCHLORINATED DIBENZOFURANS (PCDF). I. RELATIONSHIP BETWEEN INDUCTIVE EFFECTS ON HEPATIC ENZYMES AND TOXICITIES OF PURE PCDF CONGENERS RETAINED IN YUSHO PATIENTS
- EFFECT OF LIVER S9 FROM 3,4,5,3', 4'-PENTACHLOROBIPHENYL-PRETREATED RATS ON THE MUTAGENIC ACTIVITY OF THE VARIOUS CARCINOGENS TOWARD SALMONELLA TYPHIMURIUM TA 98
- Metabolism in Vivo of 3,4,5,3', 4'-Pentachlorobiphenyl and Toxicological Assessment of the Metabolite in Rats
- Acute Toxicity and Inductive Effect on Liver Enzymes of 3,4,5,3', 4'-Pentachlorobiphenyl in Chickens (Regular Presentations) (Proceedings of the 11 th Symposium on Environmental Pollutants and Toxicology)
- STUDIES ON CIS-TRANS ISOMERIZATION OF NITROFURAN DERIVATIVES BY BACTERIAL NITROREDUCTASES
- STUDIES ON THE METABOLISM OF NITROFURAN DERIVATIVES IN BACTERIA : PROPERTIES OF CIS-TRANS ISOMERASES AND NITROREDUCTASES, AND RELATIONSHIP OF THESE ENZYMES
- STUDIES ON ENZYMIC CIS-TRANS ISOMERIZATION OF NITROTHIOPHENE AND NITROBENZENE DERIVATIVES
- Reduction of the Toxicity of 2, 3, 7, 8-Tetrachlorodibenzo-p-dioxin in Mice Using an Antiulcer Drug, Geranylgeranylacetone(Toxicology)
- Enhanced Elimination of Theophylline, Phenobarbital and Strychnine from the Bodies of Rats and Mice by Squalane Treatment
- PURIFICATION AND CHARACTERIZATION ON 3,4,5,3', 4'-PENTACHLOROBIPHENYL-INDUCIBLE CYTOCHROME P-450 IN CHICKEN LIVER
- Mechanisms of Stimulated Fecal Excretion of Polychlorinated Aromatic Hydrocarbons in Rats
- Metabolic Activation and Detoxication of Polychlorinated Biphenyls
- IN VIVO METABOLITES OF 3,4,3', 4', -TETRACHLOROBIPHENYL AND THE TOXICOLOGICAL ASSESSMENT IN RATS
- OXYGEN-INSENSITIVE NITROFURAN REDUCTASES IN SALMONELLA TYPHIMURIUM TA100
- ISOLATION AND IDENTIFICATION OF THE METABOLITE OF N-(5-NITRO-2-FURFURYLIDENE)-3-AMINO-2-OXAZOLIDONE (FURAZOLI-DONE)
- Induction of a High-Spin Form of Cytochrome P-450 by Highly Toxic Polychlorinated Aromatic Hydrocarbons (Proceedings of the 14th Symposium on Environmental Pollutants and Toxicology)
- Cellular Uptake of 2,3,4,7,8-Pentachlorodibenzofuran in the Rat Liver (Proceedings of the 12 th Symposium on Environmental Pollutants and Toxicology) (Regular Presentations)
- ACCUMULATION, EXCRETION AND EFFECTS ON HEPATIC ENZYMES OF POLYCHLORINATED QUATERPHENYL CONGENERS IN RATS
- Intracellular Distribution and Binding to Cytosolic Protein of 2,3,4,7,8-Pentachlorodibenzofuran in the Liver of Rats (Regular Presentations) (Proceedings of the 11 th Symposium on Environmental Pollutants and Toxicology)
- HIGH ACCUMULATION OF 2,3,4,7,8-PENTACHLORODIBENZOFURAN TO HEPATIC MICROSOMES OF RATS
- Extremely High Affinity of 2,3,4,7,8-Pentachlorodibenzofuran for Hepatic Microsomes of Rats (Regular Presentations) (Proceedings of the 10 th Symposium on Environmental Pollutants and Toxicology)
- Effect of 3-Methylcholanthrene-and Phenobarbital-Type Polychlorinated Biphenyls (PCBs) on the Liver Soluble Enzymes of Rats (Regular Presentations) (Proceedings of the 9th Symposium on Environmental Pollutants and Toxicology)
- Enhancement of Reduction Activity of 4NQO in Animals pretreated with 3-Methylcholanthrene-type PCB and PCDF (Regular Presentations) (Proceedings of the 8th Symposium on Environmental Pollutants and Toxicology)
- Effects of dioxins on stress-responsive systems and their relevance to toxicity
- Cytochrome P450 1A1 (CYP1A1) Inhibitor α-Naphthoflavone Interferes with UDP-Glucuronosyltransferase (UGT) Activity in Intact but Not in Permeabilized Hepatic Microsomes from 3-Methylcholanthrene-Treated Rats : Possible Involvement of UGT-P450 Interactions
- The Induction of Hepatic Selenium-Binding Protein by Aryl Hydrocarbon (Ah)-Receptor Ligands in Rats
- Role of the Dioxin-like Toxic Compound Coplanar Polychlorinated Biphenyl, 3, 3', 4, 4', 5-Pentachlorobiphenyl in Reducing Hepatic Alcohol Dehydrogenase Levels in Rats in Vivo
- Enzymatic Hydroxylation of Tetrachlorobiphenyls in Rats
- Metabolism in Vitro of 3,4,3', 4'- and 2,5,2', 5'-Tetrachlorobiphenyl by Rat Liver Microsomes and Highly Purified Cytochrome P-450
- Liver Cytochrome P-450 Isozyme Responsible for the Metabolism of Tetrachlorobiphenyls in Rat (Proceedings of the 16 th Symposium on Environmental Pollutants and Toxicology)
- Inhibition of Cytochrome P-448H Dependent Catalytic Activity by 3,4,5,3', 4'-Pentachlorobiphenyl (Regular Presentations) (Proceedings of the 15 th Symposium on Environmental Pollutants and Toxicology)
- INDUCTION OF RAT HEPATIC CYTOCHROMES P450 BY TOXIC INGREDIENTS IN PLANTS : LACK OF CORRELATION BETWEEN TOXICITY AND INDUCTIVE ACTIVITY
- EFFECT OF CO-ADMINISTRATION OF INTERFERON INDUCER, POLYRIBOINOSINIC ACID-POLYRIBOCYTIDYLIC ACID, WITH SKF 525-A ON HEPATIC DRUG METABOLIZING ENZYMES OF RATS
- SUPPRESSIVE MECHANISM OF INTERFERON INDUCER, POLYRIBOINOSINIC ACID-POLYRIBOCYTIDYLIC ACID, ON THE INDUCTION OF CYTOCHROME P-450 IN RAT LIVER MICROSOMES
- SUPPRESSIVE EFFECT OF INTERFERON INDUCER, POLYRIBOINOSINIC ACID-POLYRIBOCYTIDYLIC ACID ON INDUCTION OF URIDINE DIPHOSPHATE-GLUCURONYLTRANSFERASES AND MONOOXYGENASES IN LIVER MICROSOMES OF RATS
- UNIQUE INDUCTION OF CYTOCHROME P-450 ISOZYMES IN RAT LIVER MICROSOMES BY TREATMENT WITH 3,4,5,3', 4'-PENTACHLOROBIPHENYL AND ITS EFFECT ON TESTOSTERONE METABOLISM
- EFFECT OF COBALTOUS CHLORIDE-TREATMENT ON DRUG METABOLIZING ENZYMES AND TOXICITES INDUCED BY METHYLCHOLANTHRENE-TYPE PCB
- SUPPRESSION BY INTERFERON INDUCER ON INDUCTION OF MONOOXYGENASES AND UDP-GLUCURONYLTRANSFERASES IN LIVER MICROSOMES OF RATS
- CORRELATION BETWEEN A UNIQUE CHANGE OF STEROID METABOLISM AND CYTOCHROME P-450 INDUCED BY PRETREATMENT WITH 3-METHYLCHOLANTHRENE-TYPE PCB AND PCDF
- SUPPRESSION OF THE INDUCTION OF RAT LIVER MONOOXYGENASES AND UDP-GLUCURONYLTRANSFERASES BY HEMATIN AND COBALTOUS CHLORIDE
- MECHANISM OF TOXICITY PRODUCED BY 3-METHYLCHOLANTHRENE-TYPE PCBS (2) : EFFECTS OF PCBS AND RELATED COMPOUNDS ON THE METABOLISM OF STEROIDS
- FORMATION OF HIGHLY ANALGESIC MORPHINE-6-GLUCURONIDE FOLLOWING PHYSIOLOGIC CONCENTRATION OF MORPHINE IN HUMAN BRAIN
- 21WA-03-2 Significant Induction of Molecular Chaperones, HSP70, HSP90 and Hop in a Rat Testis Cell by Very Low Level of Dioxins.
- NOVEL COLUMN CHROMATOGRAPHY PROCEDURE FOR THE PURIFICATION OF UDP-GLUCURONYLTRANSFERASES
- EFFECT OF ENDOTOXIN ON INDUCTION OF MONOOXYGENASES AND UDP-GLUCURONYLTRANSFERASES IN RAT HEPATIC MICROSOMES
- Species Difference of Site-Selective Glucuronidation of Morphine
- Species Difference in Codeine Uridine Diphosphate-Glucuronyltransferase Activity of Liver Microsomes
- SPECIES DIFFERENCE OF SITE-SELECTIVE GLUCURONIDATION OF MORPHINE
- DECREASED URINARY EXCRETION OF THIAMINE PROPYL DISULFIDE METABOLITES IN PATIENTS WITH LIVER DISEASE
- Significant Suppression of Aldolase B, Carbonic Anhydrase III and Alcohol Dehydrogenase in Liver Cytosol of Rats Treated with a Highly Toxic Coplanar PCB (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
- Effect of Highly Toxic Coplanar PCB on Peroxisomal Enzyme Activity : The Species Difference between Rats and Guinea Pigs (Proceedings of the 20th Symposium on Toxicology and Environmental Health)
- Brucine as a Potent Inducer of CYP2B3,the Third Member of the CYP2B Subfamily P450 in Rats
- Suppression of Carbonic Anhydrase III mRNA Level by an Aryl Hydrocarbon Receptor Ligand in Primary Cultured Hepatocytes of Rat(Toxicology)
- Metabolism of Drugs of Abuse : Its Contribution to the Toxicity and the Inter-Individual Differences in Drug Sensitivity
- An Improved Method for the Purification and Characterization of a 54 kDa Protein in Rat Liver Which Has Recently Been Identified as a Selenium-Binding Protein
- Effect of Dioxins on Molecular Chaperones HSP70 and HSP90 in Rat Leydig Cells(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)
- The Role of a Rat Liver Cytosolic 54 kDa Protein That is Inducible by Dioxins(PROCEEDINGS OF 24TH SYMPOSIUM ON TOXICOLOGY AND ENVIRONMENTAL HEALTH)
- Study of the Physiological Role of 3,3', 4,4', 5-Pentachlorobiphenyl Inducible 54 kDa Protein in Cytosol of Rat Liver (Proceedings of the 23rd Symposium on Toxicology and Environmental Health)
- DEAMINATION OF AMPHETAMINES BY CYTOCHROMES P450: STUDIES ON SUBSTRATE SPECIFICITY AND REGIOSELECTIVITY WITH MICROSOMES AND PURIFIED CYP2C SUBFAMILY ISOZYMES
- A UNIQUE CHANGE OF STEROID METABOLISM IN RAT LIVER MICROSOMES INDUCED WITH HIGHLY TOXIC POLYCHLORINATED BIPHENYL(PCB) AND POLYCHLORINATED DIBENZOFURAN(PCDF)
- CHEMICAL ANALYSIS AND TOXICITY OF POLYCHLORINATED BIPHENYLS AND DIBENZOFURANS IN RELATION TO YUSHO
- DIFFERENT RESPONSIVENESS OF HEPATIC AND PULMONARY MICROSOMAL MIXED FUNCTION OXIDASES TO PHENOBARBITALTYPE AND 3-METHYLCHOLANTHRENE-TYPE POLYCHLORINATED BIPHENYLS IN RATS
- MECHANISM OF TOXICITY PRODUCED BY 3-METHYLCHOLAN-THRENE-TYPE PCBs (1)
- THE MECHANISM OF N-DEMETHYLATION OF METHAMPHETAMINE BY LIVER MICROSOMES : THE ROLE OF FLAVIN CONTAINING MONOOXYGENASE AND CYTOCHROME P-450 SYSTEMS
- METABOLISM AND NEPHROTOXICITY OF PHENACETIN AND SULFANILAMIDE
- METABOLISM AND NEPHROTOXICITY OF PHENACETIN AND SULFANILAMIDE
- ENHANCEMENT OF SULFANILAMIDE N^4-HYDROXYLASE ACTIVITY IN KIDNEY AND LIVER MICROSOMES OF RATS BY PRETREATMENT WITH 3-METHYLCHOLANTHRENE TYPE-POLY-CHLORINATED BIPHENYL
- 120. OXIDATIVE ENZYME SYSTEM OF 11-HYDROXY Δ^8-THC (ACTIVE METABOLITE OF Δ^8-THC) IN HEPATIC MICROSOMES (The Third Meeting for the Study of Toxic Effect)
- Induction of Bilirubin UDP-Glucuronyltransferase and P-450 4A Subfamily in Guinea Pigs by Treatment with Coplanar PCB (Proceedings of the 18th Symposium on Toxicology, and Environmental Health)
- Enhancement of Acetaminophen Cytotoxicity in Selenium-binding Protein-overexpressed COS-1 Cells
- Effect of Coplanar PCB on Gluconeogenesis and Lipid Metabolism : Comparison between Rats and Guinea Pigs (Proceedings of the 19th Symposium on Toxicology and Environmental Health)
- SPECIES DIFFERENCE OF UDP-GLUCURONYLTRANSFERASE ISOZYMES IN LIVER MICROSOMES
- Stimulating Effect of Liquid Paraffin and Cholestyramine on Fecal Excretion of 2,3,4,7,8-Pentachlorodibenzofuran in Rats (Proceedings of the 12 th Symposium on Environmental Pollutants and Toxicology) (Regular Presentations)
- UDP-GLUCURONYLTRANSFERASES IN MICE BRAIN AND THE INDUCIBILITY
- B-16 SUBSTRATE SPECIFICITY OF PURIFIED FAD-MONOOXYGENASE TOWARD MORPHINE AND COCAINE CONGENERS
- Effect of Highly Toxic 3,3', 4,4', 5-Pentachlorobiphenyl on the Synthesis of Unsaturated Fatty Acids (Proceedings of the 22nd Symposium on Toxicology and Environmental Health)
- MORPHINE CONJUGATES AS PHARMACOLOGICALLY ACTIVE METABOLITES