Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
(-CIS-3,5-DIMETHYL-2-(3-PYRIDYL) THIAZOLIDIN-4-ONE HYDROCHLORIDE (SM-12502) AS A NOVEL SUBSTRATE FOR CYTOCHROME-P450 2A6 IN HUMAN LIVER-MICROSOMES())
Autore:
NUNOYA KI; YOKOI T; KIMURA K; KODAMA T; FUNAYAMA M; INOUE K; NAGASHIMA K; FUNAE Y; SHIMADA N; GREEN C; KAMATAKI T;
Indirizzi:
HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB,N12W6 SAPPORO HOKKAIDO 060 JAPAN HOKKAIDO UNIV,FAC PHARMACEUT SCI,DIV DRUG METAB SAPPORO HOKKAIDO 060 JAPAN HOKKAIDO UNIV,FAC MED,DEPT PATHOL SAPPORO HOKKAIDO 060 JAPAN SUMITOMO PHARMACEUT CO LTD,CLIN RES & DEV DIV OSAKA JAPAN HOKKAIDO ASSOC MED SERV WORKERS SAPPORO HOKKAIDO JAPAN SAPPORO MED UNIV,SCH MED,DEPT FORENS MED SAPPORO HOKKAIDO JAPAN HOKKAIDO UNIV HOSP,DEPT PATHOL SAPPORO HOKKAIDO JAPAN OSAKA CITY UNIV,SCH MED,CHEM LAB OSAKA 545 JAPAN DAIICHI PURE CHEM CO LTD,TOKAI RES LABS IBARAKI OSAKA JAPAN SRI INT,TOXICOL LAB MENLO PK CA 94025
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 2, volume: 277, anno: 1996,
pagine: 768 - 774
SICI:
0022-3565(1996)277:2<768:(TH(>2.0.ZU;2-W
Fonte:
ISI
Lingua:
ENG
Soggetto:
RAT HEPATIC MICROSOMES; SACCHAROMYCES-CEREVISIAE; COUMARIN 7-HYDROXYLATION; METABOLIC-ACTIVATION; ENZYMES; PURIFICATION; NITROSAMINE; EXPRESSION; OXIDATION; CDNA;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
K.I. Nunoya et al., "(-CIS-3,5-DIMETHYL-2-(3-PYRIDYL) THIAZOLIDIN-4-ONE HYDROCHLORIDE (SM-12502) AS A NOVEL SUBSTRATE FOR CYTOCHROME-P450 2A6 IN HUMAN LIVER-MICROSOMES())", The Journal of pharmacology and experimental therapeutics, 277(2), 1996, pp. 768-774

Abstract

+)-cis-3,5-dimethyl-2-(3-pyridyl)thiazolidin-4-one hydrochloride (SM-12502) was oxidized by human liver microsomes to produce the S-oxide as a sole metabolite. Indirect evidence suggested that the S-oxidation was catalyzed by cytochrome P450 (CYP). Eadie-Hofstee plots showed biphasic pattern, suggesting that at least two enzymes were involved in the S-oxidation in human liver microsomes. Kinetic parameters of the S-oxidase with high-affinity showed K-m and V-max values of 20.9 +/- 4.4mu M and 0.111 +/- 0.051 nmol/min/mg microsomal protein, respectively. The S-oxidase activity was inhibited by coumarin and anti-CYP2A antibody. Among the contents of forms of CYP in 20 samples of human liver microsomes, the content of CYP2A6 correlated with S-oxidase activity measured with 50 mu M SM-12502 (r = .808, P < .0005). A close correlation (r = .908, P < .0001) was observed between activities of SM-12502 S-oxidase and coumarin 7-hydroxylase. Microsomes from genetically engineered human B-lymphoblastoid cells expressing CYP2A6 metabolized SM-12502 to the S-oxide efficiently. The results indicate that CYP2A6 isozyme is a major form of CYP responsible for the S-oxidation of SM-12502 in human liver micosomes. Thus, SM-12502 will be a useful tool in further research to analyze a human genetic polymorphism of CYP2A6.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 03/07/20 alle ore 16:31:06