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Titolo:
ROLE OF HUMAN CYTOCHROME P4502A6 IN C-OXIDATION OF NICOTINE
Autore:
NAKAJIMA M; YAMAMOTO T; NUNOYA K; YOKOI T; NAGASHIMA K; INOUE K; FUNAE Y; SHIMADA N; KAMATAKI T; KUROIWA Y;
Indirizzi:
SHOWA UNIV,SCH PHARMACEUT SCI,DEPT CLIN PHARM,SHINAGAWA KU,1-5-8 HATANODAI TOKYO 142 JAPAN SHOWA UNIV,SCH PHARMACEUT SCI,DEPT CLIN PHARM,SHINAGAWA KU TOKYO 142 JAPAN HOKKAIDO UNIV,DIV DRUG METAB,FAC PHARMACEUT SCI SAPPORO HOKKAIDO 060 JAPAN HOKKAIDO UNIV,FAC MED,DEPT PATHOL SAPPORO HOKKAIDO 060 JAPAN HOKKAIDO UNIV HOSP,DEPT PATHOL SAPPORO HOKKAIDO JAPAN OSAKA CITY UNIV,SCH MED,CHEM LAB OSAKA 545 JAPAN TOKAI RES LABS TOKAI IBARAKI JAPAN DAIICHI PURE CHEM CO LTD TOKAI IBARAKI JAPAN
Titolo Testata:
Drug metabolism and disposition
fascicolo: 11, volume: 24, anno: 1996,
pagine: 1212 - 1217
SICI:
0090-9556(1996)24:11<1212:ROHCPI>2.0.ZU;2-O
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN LIVER-MICROSOMES; CIGARETTE-SMOKING; COUMARIN 7-HYDROXYLATION; MESSENGER-RNAS; RAT-LIVER; METABOLISM; IDENTIFICATION; PURIFICATION; SEQUENCE; (S)-NICOTINE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
37
Recensione:
Indirizzi per estratti:
Citazione:
M. Nakajima et al., "ROLE OF HUMAN CYTOCHROME P4502A6 IN C-OXIDATION OF NICOTINE", Drug metabolism and disposition, 24(11), 1996, pp. 1212-1217

Abstract

Nicotine is primarily metabolized to cotinine in humans. In this study, human cytochrome P450 (CYP) isoform involved in cotinine formation was identified. The formation of cotinine in 10 human liver microsomeswas determined with a 50 mu M nicotine concentration and with a cytosol preparation as a source of aldehyde oxidase. Cotinine formation in human liver microsomes significantly correlated with immunochemically determined CYP2A6 levels (r=0.663, p<0.05), coumarin 7-hydroxylase activities (r=0.831, p<0.01), and cotinine 3'-hydroxylase activities (r=0.735, p<0.01) that are responsible for CYP2A6. In inhibition studies, cotinine formation in human liver microsomes was inhibited by coumarinand rabbit anti-rat CYP2A1 antibody specifically. When the capabilityof microsomes of B-lymphoblastoid cells expressing human CYPs to perform biotransformation of nicotine to cotinine was determined, cDNA-expressed CYP2A6 exhibited the highest cotinine formation. The K-Mapp values from microsome expressing CYP2A6 cDNA were similar to the value obtained from human liver microsomes. The large interindividual variabilities in cotinine formation and immunochemically determined CYP2A6 levels were observed in human liver microsomes, suggesting genetic polymorphism of CYP2A6. Nicotine is a new in vivo probe for phenotyping of CYP2A6 in humans.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 13/07/20 alle ore 20:24:25