5‐Hydroxytryptamine is biotransformed by CYP2C9, 2C19 and 2B6 to hydroxylamine, which is converted into nitric oxide

作者: Caroline Fradette , Nobuharu Yamaguchi , Patrick Du Souich

DOI: 10.1038/SJ.BJP.0705632

关键词: CYP1A2BiochemistryChemistryCytochrome P450Cytochrome P-450 CYP2B6CYP2B6CatalaseNitric oxideOxidase testHydroxylamine

摘要: There is circumstantial evidence suggesting that 5-hydroxytryptamine (5-HT) could be biotransformed by enzymatic systems other than monoamino oxidase A, and the isoforms of cytochrome P450 may a source nitric oxide. This study aimed to assess whether contributes 5-HT biotransformation, provide metabolism generates oxide. Addition cultured hepatocytes yielded 5-hydroxyindol acetic acid, formation modulated enzyme inducers inhibitors. Recombinant human CYP2B6, 2C9 2C19 in but not CYP1A2, 2D6 or 3A4. Cultured with generated oxide, amount which was altered In presence 2C19, relaxed precontracted isolated aortic rings, without endothelium, an effect prevented addition methylene blue inhibitor catalase, myoglobin. absence hydroxylamine always assayed as byproduct metabolism. In conclusion, biotransform 5-HT, yielding hydroxylamine, converted oxide catalase. British Journal Pharmacology (2004) 141, 407–414. doi:10.1038/sj.bjp.0705632

参考文章(52)
Ignarro L, Barry Bk, Gruetter Ca, McNamara Db, Kadowitz Pj, Gruetter Dy, Relaxation of bovine coronary artery and activation of coronary arterial guanylate cyclase by nitric oxide, nitroprusside and a carcinogenic nitrosoamine. Journal of cyclic nucleotide research. ,vol. 5, pp. 211- ,(1979)
M O López-Figueroa, A L López-Figueroa, T M McLeod, Nitric oxide, stress, and depression. Psychopharmacology Bulletin. ,vol. 35, pp. 24- 41 ,(2001)
Per O. Seglen, Preparation of isolated rat liver cells. Methods in Cell Biology. ,vol. 13, pp. 29- 83 ,(1976) , 10.1016/S0091-679X(08)61797-5
Selda Emre-Aydıngöz, Meral Tuncer, Saban Remzı Erdem, Relaxation induced by serotonin and sumatriptan in isolated guinea pig gallbladder strips. Research in Experimental Medicine. ,vol. 200, pp. 175- 182 ,(2001)
Matthew B. Grisham, Glenda G. Johnson, Jack R. Lancaster, Quantitation of nitrate and nitrite in extracellular fluids Methods in Enzymology. ,vol. 268, pp. 237- 246 ,(1996) , 10.1016/S0076-6879(96)68026-4
B PEARSONMURPHY, Antiglucocorticoid therapies in major depression: A review Psychoneuroendocrinology. ,vol. 22, pp. S125- S132 ,(1997) , 10.1016/S0306-4530(97)00021-8
Beate Fisslthaler, Rüdiger Popp, Ladislau Kiss, Michael Potente, David R. Harder, Ingrid Fleming, Rudi Busse, Cytochrome P450 2C is an EDHF synthase in coronary arteries Nature. ,vol. 401, pp. 493- 497 ,(1999) , 10.1038/46816
A. Lewis Farr, Oliver H. Lowry, Rose J. Randall, Nira J. Rosebrough, Protein Measurement with the Folin Phenol Reagent Journal of Biological Chemistry. ,vol. 193, pp. 265- 275 ,(1951)
Richard J. Roman, P-450 Metabolites of Arachidonic Acid in the Control of Cardiovascular Function Physiological Reviews. ,vol. 82, pp. 131- 185 ,(2002) , 10.1152/PHYSREV.00021.2001