Ambient tonicity and intestinal cytochrome CYP3A

Abstract

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.

Keywords::

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

Acknowledgements

AI Chuang is supported by the Ontario Graduate Scholarship, SickKids Restracomp Studentship and the Canadian Institute for Health Research Doctoral Research Award. The study is funded by the Canadian Institute of Health Research.

Notes

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