Enteroendocrine and Neuronal Mechanisms in Pathophysiology of Acute Infectious Diarrhea
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While enterocyte secretion is the predominant mechanism considered responsible for secretory diarrhea in response to acute enteric infections, there are several lines of evidence that support alternative mechanisms controlling fluid and electrolyte secretion in diarrhea.
To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea.
Acute infectious diarrheas due to bacterial toxins (e.g., cholera, E. coli heat-stable enterotoxin, C. difficile) and rotavirus are all associated with secretion of transmitters from enteroendocrine cells (e.g., 5-HT) and activation of afferent neurons that stimulate submucosal secretomotor neurons. The latter secrete acetylcholine (which binds to muscarinic receptors on epithelial cells) and VIP. Involvement of nerves was demonstrated by inhibition of bacterial toxin-induced secretion by hexamethonium (nicotinic), tetrodotoxin (Na+ channel blocker), and lidocaine (visceral/mucosal afferents). Nicotinic receptors are present on secretomotoneurons and these are activated by release of acetylcholine from enteric interneurons or extrinsic efferent fibers. Specific organisms also modify other mechanisms that may contribute to development of acute diarrhea. Thus, mucin secretion, activation of motor mechanisms, increased mucosal permeability and inhibition of bile acid absorption have been reported in specific types of acute infectious diarrhea.
New therapies targeting neural and transmitter mediation including 5-HT, VIP, NPY, as well as toxin receptors and channels activated during acute infectious diarrhea could usher in a novel approach to enhancing glucose–electrolyte solutions used in the treatment of acute diarrhea.
KeywordsChannel Chloride Cholera CFTR Goblet cell Guanylin
Cyclic adenosine monophosphate
Cystic fibrosis transmembrane conductance regulator
Cyclic guanosine monophosphate
Calcitonin gene-related peptide
Guanylate cyclase C
Ganglioside membrane receptor
Migrating action potential complex
E. coli heat-stable enterotoxin
Vasoactive intestinal peptide