کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2514494 1118469 2009 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Coordinate regulation of human drug-metabolizing enzymes, and conjugate transporters by the Ah receptor, pregnane X receptor and constitutive androstane receptor
موضوعات مرتبط
علوم پزشکی و سلامت داروسازی، سم شناسی و علوم دارویی داروشناسی
پیش نمایش صفحه اول مقاله
Coordinate regulation of human drug-metabolizing enzymes, and conjugate transporters by the Ah receptor, pregnane X receptor and constitutive androstane receptor
چکیده انگلیسی

Coordinate regulation of Phase I and II drug-metabolizing enzymes and conjugate transporters by nuclear receptors suggests that these proteins evolved to an integrated biotransformation system. Two major groups of ligand-activated nuclear receptors/xenosensors evolved: the Ah receptor (activated by aryl hydrocarbons and drugs such as omeprazole) and type 2 steroid receptors such as PXR and CAR, activated by drugs such as rifampicin, carbamazepin and phenytoin. It is increasingly recognized that there is considerable cross-talk between these xenosensors. Therefore, an attempt was made to discuss biotransformation by the Ah receptor together with that of PXR and CAR. Due to considerable species differences the emphasis is on human biotransformation. Agonists coordinately induce biotransformation due to common xenosensor-binding response elements in the regulatory region of target genes. However, whereas different groups of xenobiotics appear to more selectively stimulate CYPs (Phase I), their regulatory control largely converged in modulating Phase II metabolism and transport. Biotransformation appears to be tightly controlled to achieve efficient homeostasis of endobiotics and detoxification of dietary phytochemicals, but nuclear receptor agonists may also lead to potentially harmful drug interactions.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical Pharmacology - Volume 77, Issue 4, 15 February 2009, Pages 689–699
نویسندگان
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