Calcimimetic Acts on Enteric Neuronal CaSR to Reverse Cholera Toxin-induced Intestinal Electrolyte Secretion

Overview

Journal Sci Rep

Specialty Science

Date 2018 May 20

PMID 29777154

Citations 7

Authors

Lieqi Tang

Lingli Jiang

Megan E McIntyre

Ekaterina Petrova

Sam X Cheng

Affiliations

Soon will be listed here.

Abstract

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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