Journal
SCIENTIFIC REPORTS
Volume 8, Issue -, Pages -Publisher
NATURE RESEARCH
DOI: 10.1038/s41598-018-26171-4
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Funding
- Eunice Kennedy Shriver National Institute of Child Health & Human Development of the National Institutes of Health [HD079674]
- Children's Miracle Network
- NIH [T32 DK 007017]
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Treatment of acute secretory diarrheal illnesses remains a global challenge. Enterotoxins produce secretion through direct epithelial action and indirectly by activating enteric nervous system (ENS). Using a microperfused colonic crypt technique, we have previously shown that R568, a calcimimetic that activates the calcium-sensing receptor (CaSR), can act on intestinal epithelium and reverse cholera toxin-induced fluid secretion. In the present study, using the Ussing chamber technique in conjunction with a tissue-specific knockout approach, we show that the effects of cholera toxin and CaSR agonists on electrolyte secretion by the intestine can also be attributed to opposing actions of the toxin and CaSR on the activity of the ENS. Our results suggest that targeting intestinal CaSR might represent a previously undescribed new approach for treating secretory diarrheal diseases and other conditions with ENS over-activation.
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