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Titolo:
THE RABBIT PULMONARY CYTOCHROME-P450 ARACHIDONIC-ACID METABOLIC PATHWAY - CHARACTERIZATION AND SIGNIFICANCE
Autore:
ZELDIN DC; PLITMAN JD; KOBAYASHI J; MILLER RF; SNAPPER JR; FALCK JR; SZAREK JL; PHILPOT RM; CAPDEVILA JH;
Indirizzi:
NIEHS,PULM PATHOBIOL LAB,POB 12233 RES TRIANGLE PK NC 27709 NIEHS,CELLULAR & MOLEC PHARMACOL LAB RES TRIANGLE PK NC 27709 VANDERBILT UNIV,SCH MED,DEPT MED NASHVILLE TN 37232 VANDERBILT UNIV,SCH MED,DEPT BIOCHEM NASHVILLE TN 37232 UNIV TEXAS,SW MED CTR,DEPT MOLEC GENET DALLAS TX 75235 MARSHALL UNIV,SCH MED,DEPT PHARMACOL HUNTINGTON WV 25755
Titolo Testata:
The Journal of clinical investigation
fascicolo: 5, volume: 95, anno: 1995,
pagine: 2150 - 2160
SICI:
0021-9738(1995)95:5<2150:TRPCAM>2.0.ZU;2-H
Fonte:
ISI
Lingua:
ENG
Soggetto:
LIVER MICROSOMAL CYTOCHROME-P-450; SPECIES-DEPENDENT EXPRESSION; CYTOSOLIC EPOXIDE HYDROLASE; EPOXYEICOSATRIENOIC ACIDS; SMOOTH-MUSCLE; RENAL-CORTEX; 12(R)-HYDROXYEICOSATRIENOIC ACID; 5,6-EPOXYEICOSATRIENOIC ACID; ENANTIOFACIAL SELECTIVITY; OXIDATIVE-METABOLISM;
Keywords:
EICOSANOID; EPOXYGENASE; EPOXYEICOSATRIENOIC ACID; DIHYDROXYEICOSATRIENOIC ACID; HYDROXYEICOSATETRAENOIC ACID;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
78
Recensione:
Indirizzi per estratti:
Citazione:
D.C. Zeldin et al., "THE RABBIT PULMONARY CYTOCHROME-P450 ARACHIDONIC-ACID METABOLIC PATHWAY - CHARACTERIZATION AND SIGNIFICANCE", The Journal of clinical investigation, 95(5), 1995, pp. 2150-2160

Abstract

Cytochrome P450 metabolizes arachidonic acid to several unique and biologically active compounds in rabbit liver and kidney, Microsomal fractions prepared from rabbit lung homogenates metabolized arachidonic acid through cytochrome P450 pathways, yielding cis-epoxyeicosatrienoicacids (EETs) and their hydration products, vic-dihydroxyeicosatrienoic acids, mid-chain cis-trans conjugated dienols, and 19- and 20-hydroxyeicosatetraenoic acids. Inhibition studies using polyclonal antibodies prepared against purified CYP2B4 demonstrated 100% inhibition of arachidonic acid epoxide formation. Purified CYP2B4, reconstituted in thepresence of NADPH-cytochrome P450 reductase and cytochrome bg, metabolized arachidonic acid, producing primarily EETs, EETs were detected in lung homogenate using gas chromatography/mass spectroscopy, providing evidence for the in vivo pulmonary cytochrome P450 epoxidation of arachidonic acid, Chiral analysis of these lung EETs demonstrated a preference for the 14(R),15(S)-, ll(S),12(R)-, and 8(S),9(R)-EET enantiomers. Both EETs and vic-dihydroxyeicosatrienoic acids were detected in bronchoalveolar lavage fluid, At micromolar concentrations, methylated 5,6-EET and 8,9-EET significantly relaxed histamine-contracted guinea pig hilar bronchi in vitro. In contrast, 20-hydroxyeicosatetraenoic acid caused contraction to near maximal tension. We conclude that CYP2B4, an abundant rabbit lung cytochrome P450 enzyme, is the primary constitutive pulmonary arachidonic acid epoxygenase and that these locally produced, biologically active eicosanoids may be involved in maintaining homeostasis within the lung.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 26/09/20 alle ore 16:07:18