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Titolo:
Inhibitory effect of nitric oxide on the induction of cytochrome P450 3A4 mRNA by 1,25-dihydroxyvitamin D-3 in Caco-2 cells
Autore:
Hara, H; Mitani, N; Adachi, T;
Indirizzi:
Gifu Pharmaceut Univ, Lab Clin Pharmaceut, Gifu 5028585, Japan Gifu Pharmaceut Univ Gifu Japan 5028585 Pharmaceut, Gifu 5028585, Japan
Titolo Testata:
FREE RADICAL RESEARCH
fascicolo: 3, volume: 33, anno: 2000,
pagine: 279 - 285
SICI:
1071-5762(2000)33:3<279:IEONOO>2.0.ZU;2-A
Fonte:
ISI
Lingua:
ENG
Soggetto:
HUMAN HEPATOCYTES; METABOLISM; EXPRESSION; ENDOTOXIN; SYNTHASE; CYCLOSPORINE; CYTOKINES;
Keywords:
nitric oxide; cytochrome P450 3A4; 1,25-dihydroxyvitamin D3; Caco-2;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
21
Recensione:
Indirizzi per estratti:
Indirizzo: Hara, H Gifu Pharmaceut Univ, Lab Clin Pharmaceut, 5-6-1 Mitahorahigashi, Gifu 5028585, Japan Gifu Pharmaceut Univ 5-6-1 Mitahorahigashi Gifu Japan 5028585 pan
Citazione:
H. Hara et al., "Inhibitory effect of nitric oxide on the induction of cytochrome P450 3A4 mRNA by 1,25-dihydroxyvitamin D-3 in Caco-2 cells", FREE RAD RE, 33(3), 2000, pp. 279-285

Abstract

Cytochrome P450 (CYP)-dependent drug metabolism decreases in vivo and in cultured hepatocytes under various immunostimulatory conditions. Nitric oxide (NO) released during inflammation is presumed to be involved in this phenomenon. CYP3A4, which is abundant in the liver and small intestine and participates in the metabolism of various drugs, is known to be induced by 1,25-dihydroxyvitamin D-3 (1.25(OH)(2)D-3) in the colon carcinoma cell line Caco-2. In this study we examined whether NO affected CYP3A4 gene expression induced by 1,25(OH)(2)D-3 in Caco-2 cells. Induction of CYP3A4 mRNA by 1,25(OH)(2)D-3 was suppressed in a dose-dependent manner by treatment with the NO donors NOR-4 (15-500 mu M) or S-nitroso-N-acetylpenicillamine (30 mu M-1 mM), which spontaneously release NO. These results indicated that NO has aninhibitory effect on the induction of CYP3A4 mRNA by 1,25(OH)(2)D-3 in Caco-2 cells. Treatment with the guanylate cyclase inhibitor ODQ failed to prevent the inhibition of induction of CYP3A4 mRNA by 1,25(OH)(2)D-3. 8-Bromo cGMP had no effect on 1,25(OH)(2)D-3-induced CYP3A4 gene expression. Therefore, the suppression of CYP3A4 mRNA by NO might be mediated through a guanylate cyclase-independent pathway.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 28/01/20 alle ore 21:09:18