Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 322, Issue 4, Pages G405-G420Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00316.2021
Keywords
chloride secretion; diarrhea; epithelial transport
Categories
Funding
- National Institutes of Health [DK28305]
- Science Foundation Ireland
- Estratest Settlement Fund
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One of the primary functions of the intestinal epithelium is to regulate the transport of fluid and electrolytes. Under normal circumstances, absorption is predominant, enabling conservation of water. However, in secretory diarrhea, excessive fluid secretion overwhelms absorption, leading to water loss in stool. This review discusses the regulation of Cl- and fluid secretion in the intestine, dysregulation in secretory diarrhea, therapeutic approaches, and innovative strategies for treating constipation by exploiting intestinal secretory mechanisms.
One of the primary functions of the intestinal epithelium is to transport fluid and electrolytes to and from the luminal contents. Under normal circumstances, absorptive and secretory processes are tightly regulated such that absorption predominates, thereby enabling conservation of the large volumes of water that pass through the intestine each day. However, in conditions of secretory diarrhea, this balance becomes dysregulated, so that fluid secretion, driven primarily by Cl- secretion, overwhelms absorptive capacity, leading to increased loss of water in the stool. Secretory diarrheas are common and include those induced by pathogenic bacteria and viruses, allergens, and disruptions to bile acid homeostasis, or as a side effect of many drugs. Here, we review the cellular and molecular mechanisms by which Cl- and fluid secretion in the intestine are regulated, how these mechanisms become dysregulated in conditions of secretory diarrhea, currently available and emerging therapeutic approaches, and how new strategies to exploit intestinal secretory mechanisms are successfully being used in the treatment of constipation.
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