Ambient tonicity and intestinal cytochrome CYP3A.
BACKGROUND
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.


METHODS
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.


RESULTS
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).


CONCLUSIONS
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.
Chuang
Andrew I
AI
Department of Pharmacology, University of Toronto, Ontario, Canada.
Ito
Shinya
S
D000818:Animals; D051544:Cytochrome P-450 CYP3A / Q000378:metabolism*; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D007413:Intestinal Mucosa / Q000201:enzymology*; D050778:NFATC Transcription Factors / Q000378:metabolism*; D009994:Osmolar Concentration; D019518:Postprandial Period; D017673:Sodium Chloride, Dietary / Q000494:pharmacology; D014158:Transcription, Genetic
D050778:NFATC Transcription Factors; D017673:Sodium Chloride, Dietary; D051544:Cytochrome P-450 CYP3A