Hydroxylase inhibition attenuates colonic epithelial secretory function and ameliorates experimental diarrhea.
AffiliationMolecular Medicine Laboratories, Royal College of Surgeons in Ireland, Beaumont, Hospital, Dublin, Ireland.
MeSHAmino Acids, Dicarboxylic/*pharmacology
Gene Expression Regulation, Enzymologic/drug effects
Mice, Inbred C57BL
Mixed Function Oxygenases/*antagonists & inhibitors
MetadataShow full item record
CitationFASEB J. 2011 Feb;25(2):535-43. Epub 2010 Oct 13.
JournalThe FASEB journal : official publication of the Federation of American Societies , for Experimental Biology
AbstractHydroxylases are oxygen-sensing enzymes that regulate cellular responses to hypoxia. Transepithelial Cl(-) secretion, the driving force for fluid secretion, is dependent on O(2) availability for generation of cellular energy. Here, we investigated the role of hydroxylases in regulating epithelial secretion and the potential for targeting these enzymes in treatment of diarrheal disorders. Ion transport was measured as short-circuit current changes across voltage-clamped monolayers of T(84) cells and mouse colon. The antidiarrheal efficacy of dimethyloxallyl glycine (DMOG) was tested in a mouse model of allergic disease. Hydroxylase inhibition with DMOG attenuated Ca(2+)- and cAMP-dependent secretory responses in voltage-clamped T(84) cells to 20.2 +/- 2.6 and 38.8 +/- 6.7% (n=16; P