Ambient tonicity and intestinal cytochrome CYP3A

作者：Chuang Andrew I; Ito Shinya^*

来源：Expert Opinion on Drug Metabolism and Toxicology, 2010, 6(8): 883-893.

DOI：10.1517/17425251003781912

• CYP3A
• first-pass metabolism
• NFAT5/TonEBP
• osmolality
• P450 drug metabolism enzymes

Importance of the field: Recently-discovered tonicity-dependence of human CYP3A expression in vitro may be a novel mechanism of CYP3A regulation in the intestinal epithelia, which exists in a dynamic osmotic environment influenced by food intake.
Areas covered in this review: A combination of focused and comprehensive literature searches to identify any relevant reports using Medline (from 1950 to 7 November 2009) through the OVID system.
What the reader will gain: An update on current knowledge on osmotic environment in the gastrointestinal (GI) tract and its impact on intestinal CYP3A expression and function with special emphasis on the tonicity-sensitive transcription factor nuclear factor of activated T cells 5 (NFAT5).
Take home message: In vitro hypertonicity of ambient osmotic environment in cultured human cells increases expression of CYP3A through transcriptional enhancement by osmosensitive NFAT5. Although post-prandial osmolality in the GI lumen in vivo is substantially increased, NFAT5 activation has not been reported. Similarly, high-salt diet increases intestinal CYP3A function in humans, but it is not known whether these changes are mediated directly by NFAT5.

• 出版日期2010-8