Digestive Diseases and Sciences

, Volume 57, Issue 1, pp 19–27

Enteroendocrine and Neuronal Mechanisms in Pathophysiology of Acute Infectious Diarrhea

Authors

    • Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), College of MedicineMayo Clinic
  • Sara Nullens
    • Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), College of MedicineMayo Clinic
  • Tyler Nelsen
    • Clinical Enteric Neuroscience Translational and Epidemiological Research (C.E.N.T.E.R.), College of MedicineMayo Clinic
Review

DOI: 10.1007/s10620-011-1939-9

Cite this article as:
Camilleri, M., Nullens, S. & Nelsen, T. Dig Dis Sci (2012) 57: 19. doi:10.1007/s10620-011-1939-9

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.

Keywords

ChannelChlorideCholeraCFTRGoblet cellGuanylin

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

Copyright information

© Springer Science+Business Media, LLC 2011