Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
A MAJOR ROLE FOR CYP2A6 IN NICOTINE C-OXIDATION BY HUMAN LIVER-MICROSOMES
Autore:
MESSINA ES; TYNDALE RF; SELLERS EM;
Indirizzi:
UNIV TORONTO,DEPT PHARMACOL,MED SCI BLDG,1 KINGS COLL CIRCLE,RM 4334 TORONTO ON M5S 1A8 CANADA UNIV TORONTO,DEPT PHARMACOL TORONTO ON M5S 1A8 CANADA ADDICT RES FDN TORONTO ON M5S 2S1 CANADA UNIV TORONTO,DEPT MED TORONTO ON CANADA UNIV TORONTO,DEPT PSYCHIAT TORONTO ON CANADA WOMENS COLL HOSP TORONTO ON M5S 1B2 CANADA
Titolo Testata:
The Journal of pharmacology and experimental therapeutics
fascicolo: 3, volume: 282, anno: 1997,
pagine: 1608 - 1614
SICI:
0022-3565(1997)282:3<1608:AMRFCI>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
LUNG-CANCER PATIENTS; DEBRISOQUINE OXIDATION; COUMARIN 7-HYDROXYLATION; POLYMORPHIC OXIDATION; GENETIC-POLYMORPHISM; NATIVE CHINESE; METABOLISM; PHENOTYPE; SUSCEPTIBILITY; POPULATION;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
51
Recensione:
Indirizzi per estratti:
Citazione:
E.S. Messina et al., "A MAJOR ROLE FOR CYP2A6 IN NICOTINE C-OXIDATION BY HUMAN LIVER-MICROSOMES", The Journal of pharmacology and experimental therapeutics, 282(3), 1997, pp. 1608-1614

Abstract

Nicotine is primarily metabolized to cotinine by cytochromes P450 (CYPs). The degree of variation in the metabolism of nicotine to cotinineand the relative roles of the polymorphic enzymes CYP2A6 and CYP2D6 in this metabolism were investigated. The apparent K-m and V-max values(mean +/- S.D.) for cotinine formation in human liver microsomes (n =31) were 64.9 +/- 32.7 mu M and 28.1 +/- 28.7 nmol/mg of protein/hr, respectively. A 30-fold difference was seen among the individual V-maxvalues, with four livers showing significantly higher rates of cotinine formation. CYP2D6 is unimportant in nicotine metabolism because quinidine (a CYP2D6 inhibitor) had little effect on inhibition of cotinine formation; V-max values for dextromethorphan (CYP2D6 probe substrate) and nicotine (n = 9) did not correlate (r = .49, P = .18), and a cDNA CYP2D6 expression system failed to metabolize nicotine to cotinine. CYP2A6 appears to be the major P450 involved in human nicotine metabolism to cotinine. Coumarin, a specific and selective CYP2A6 substrate, competitively inhibited cotinine formation by 85 +/- 11% (mean +/- S.D.) in 31 human livers. The K-i value for this inhibition ranged from 1to 5 mu M, and a CYP2A6 monoclonal antibody inhibited cotinine formation by >75%. Immunochemically determined CYP2A6 correlated significantly with nicotine-to-cotinine V-max values (r = .90, n = 30, P < .001) and to inhibition of nicotine metabolism by coumarin (r = .94, n = 30,P < .001). These data indicate that nicotine metabolism is highly variable among individual livers and that this is due to variable expression of CYP2A6, not CYP2D6.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 19:02:42