TY - JOUR
T1 - Enteroendocrine and neuronal mechanisms in pathophysiology of acute infectious diarrhea
AU - Camilleri, Michael
AU - Nullens, Sara
AU - Nelsen, Tyler
N1 - Funding Information:
Acknowledgments Dr. M. Camilleri is funded by grant RO1-DK079866 from National Institutes of Health. The excellent secretarial support of Mrs. Cindy Stanislav is gratefully acknowledged.
PY - 2012/1
Y1 - 2012/1
N2 - Background: 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. Aim: To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea. Recent Advances: 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. Conclusion: 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.
AB - Background: 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. Aim: To review enteroendocrine and neuronal mechanisms that participate in the development of acute infectious diarrhea. Recent Advances: 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. Conclusion: 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.
KW - CFTR
KW - Channel
KW - Chloride
KW - Cholera
KW - Goblet cell
KW - Guanylin
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U2 - 10.1007/s10620-011-1939-9
DO - 10.1007/s10620-011-1939-9
M3 - Review article
C2 - 22001941
AN - SCOPUS:84856765201
SN - 0163-2116
VL - 57
SP - 19
EP - 27
JO - Digestive diseases and sciences
JF - Digestive diseases and sciences
IS - 1
ER -