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Enteroendocrine and Neuronal Mechanisms in Pathophysiology of Acute Infectious Diarrhea

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Abstract

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.

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Abbreviations

5-HT:

Serotonin

ACh:

Acetyl choline

BAC:

Benzalkonium chloride

cAMP:

Cyclic adenosine monophosphate

CFTR:

Cystic fibrosis transmembrane conductance regulator

cGMP:

Cyclic guanosine monophosphate

CGRP:

Calcitonin gene-related peptide

CT:

Cholera toxin

GCC:

Guanylate cyclase C

GM1 :

Ganglioside membrane receptor

IFN:

Interferon

Isc:

Short-circuit current

MAPC:

Migrating action potential complex

NK1 :

Neurokinin 1

NPY:

Neuropeptide Y

STa:

E. coli heat-stable enterotoxin

TTX:

Tetrodotoxin

VIP:

Vasoactive intestinal peptide

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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.

Conflict of interest

There are no relevant financial conflicts of interest.

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Authors and Affiliations

  1. Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), College of Medicine, Mayo Clinic, Charlton 8-110, 200 First St. S.W., Rochester, MN, 55905, USA

    Michael Camilleri, Sara Nullens & Tyler Nelsen

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  1. Michael Camilleri
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  2. Sara Nullens
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Correspondence to Michael Camilleri.

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Camilleri, M., Nullens, S. & Nelsen, T. Enteroendocrine and Neuronal Mechanisms in Pathophysiology of Acute Infectious Diarrhea. Dig Dis Sci 57, 19–27 (2012). https://doi.org/10.1007/s10620-011-1939-9

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