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. 2012 Mar;142(3):e1-9.
doi: 10.1053/j.gastro.2012.01.014. Epub 2012 Jan 20.

Translational approaches for pharmacotherapy development for acute diarrhea

Mark Donowitz  1 , David H Alpers, Henry J Binder, Thomas Brewer, Jill Carrington, Michael J Grey
Affiliations

Translational approaches for pharmacotherapy development for acute diarrhea

Mark Donowitz et al. Gastroenterology. 2012 Mar.
No abstract available

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Conflict of interest statement

Conflicts of interest

These authors disclose the following: Mark Donowitz is partial owner of Tranzmembrane, Inc, which holds the patent for the human NHE3 gene. The remaining authors disclose no conflicts.

Figures

Figure 1
Figure 1
Host physiologic processes contributing to acute diarrhea susceptibility and pathophysiology. Although the colon has a distinct morphology and function, similar processes and factors are present. The epithelial barrier, with its glycocalyx and mucus layer, serves to separate both the commensal and pathogenic microbiota from the underlying lamina propria. This epithelium is maintained and renewed continually from stem cells. In addition, the epithelial cells interact with immune cells and myofibroblasts from the lamina propria. The immune interactions with the epithelium and in the lamina propria are tightly controlled to allow commensal bacteria to colonize the gut, but combat infections that cause diarrhea. Electrolyte transport by the epithelium drives fluid movement. Transport is mediated by cell-surface transport proteins on the apical and basolateral surfaces of the enterocytes. Insets illustrate ion channel transport in representative jejunal sodium absorptive cells (inset: small intestinal Na+ absorptive cell), a small intestinal and colonic crypt chloride secretory cell (inset: Cl− secretory cell [in crypt of small intestine and colon]) and a colonic sodium absorptive cell (inset: colonic Na+ absorptive cell). Specific transporters and/or their regulatory factors may be considered as targets for therapy development. Tight junctions (TJ), also play an important role in regulating paracellular transport of electrolytes and water. Specialized enteroendocrine cells may also contribute to control of electrolyte and fluid transport. The enteric nervous system innervates both the epithelium, influencing transport, and the smooth muscle, influencing motility. Each villus is supplied with blood vessels and lymphatics, in addition to the other components of the lamina propria. Research to understand not only the individual components, but the integrated roles of these many cells and tissues in health and in acute diarrhea will likely be needed to achieve development of effective antidiarrheal therapies. Figure derived from Binder HJ. Causes of chronic diarrhea. N Engl J Med 2006;355:236–239.
See this image and copyright information in PMC

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