کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
9001466 | 1118521 | 2005 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Serotonin glucuronidation by Ah receptor- and oxidative stress-inducible human UDP-glucuronosyltransferase (UGT) 1A6 in Caco-2 cells
دانلود مقاله + سفارش ترجمه
دانلود مقاله ISI انگلیسی
رایگان برای ایرانیان
کلمات کلیدی
5-HT4-methylumbelliferoneMUFTBHQUGTBNF5-hydroxytryptamineTCDDtert-butylhydroquinoneNQO12,3,7,8-Tetrachlorodibenzo-p-dioxin - 2،3،7،8-تترا کلریدیبنزوپتوفان دیوکسینMTT - MTTNAD(P)H:quinone oxidoreductase 1 - NAD (P) H: کینون اکسیدوردوکتاز 1UDP-glucuronosyltransferase - UDP-گلوکورونوسیل ترانسفرازβ-naphthoflavone - β-naftoflavoneOxidative stress - تنش اکسیداتیوThymoquinone - تیموکینونSerotonin - سروتونین
موضوعات مرتبط
علوم پزشکی و سلامت
داروسازی، سم شناسی و علوم دارویی
داروشناسی
پیش نمایش صفحه اول مقاله
![عکس صفحه اول مقاله: Serotonin glucuronidation by Ah receptor- and oxidative stress-inducible human UDP-glucuronosyltransferase (UGT) 1A6 in Caco-2 cells Serotonin glucuronidation by Ah receptor- and oxidative stress-inducible human UDP-glucuronosyltransferase (UGT) 1A6 in Caco-2 cells](/preview/png/9001466.png)
چکیده انگلیسی
Caco-2 cells are a widely used model in drug development to study intestinal drug transport and metabolism. Recently, serotonin (5-hydroxytryptamine, 5-HT) has been characterized as a highly selective substrate of human UDP-glucuronosyltransferase UGT1A6 [Krishnaswamy S, Duan SX, von Moltke LL, Greenblatt DJ, Court MH. Validation of serotonin (5-hydroxytryptamine) as an in vitro substrate probe for human UDP-glucuronosyltransferase (UGT) 1A6. Drug Metab Disp 2003; 31:133-9], an isoform which conjugates planar phenols and is inducible by Ah receptor agonists and by oxidative/electrophile stress. To gain more insight into intestinal 5-HT disposition, uptake and metabolism of this neurotransmitter was studied in Caco-2 cell monolayers. It was found that 5-HT was taken up from the basolateral and to a lesser extent from the apical surface. It was mainly excreted basolaterally as 5-HT glucuronide. 5-HT UGT activity and UGT1A6 mRNA were induced by Ah receptor agonists and by oxidative stress generated by tert-butylhydroquinone and by isomeric thymoquinone, a potential antitumor agent and constituent of Nigella sativa seeds, commonly used as a condiment in the Middle East. While UGT1A6 induction was clearly detectable in NAD(P)H:quinone oxidoreductase 1 (NQO1)-deficient Caco-2 cells, it was not induced in NQO1-efficient HT-29 colon adenocarcinoma cells. The results suggest that - in addition to its detoxification function - intestinal UGT1A6 contributes to intestinal homeostasis of 5-HT from dietary sources and from release by enterochromaffin cells.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 69, Issue 9, 1 May 2005, Pages 1397-1402
Journal: Biochemical Pharmacology - Volume 69, Issue 9, 1 May 2005, Pages 1397-1402
نویسندگان
Christoph Köhle, Osama A. Badary, Karl Nill, Barbara S. Bock-Hennig, Karl Walter Bock,