Phenotypic differences in cholinergic responses of distal colonic epithelium

Prior, Todd; Hernandez, Jeremy M.; Tougas, Gervais; Rangachari, P. K.

doi:10.1113/expphysiol.2003.026989

Cited by 1 publication

(2 citation statements)

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“…Also, CCh‐ and BCh‐evoked Δ I SC in the rat small intestine are TTX insensitive (Przyborski and Levin, 1997), whereas, in the rat colon, I SC responses to several AChR agonists, including ACh and CCh, are reduced by TTX (O'Malley et al , 1995). Along with the species and regional differences in TTX sensitivity to cholinergically mediated ion transport, there is further evidence that should caution against making broad conclusions based on individual studies: Prior et al (2004) showed that colonic tissue from two lines of the Flinders strain of rats have different TTX sensitivities to CCh‐induced increases in I SC .…”

Section: Cholinergic Control Of Enteric Epithelial Ion Transportmentioning

confidence: 99%

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Cholinergic regulation of epithelial ion transport in the mammalian intestine

Hirota

McKay

2006

British J Pharmacology

119

110

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Acetylcholine (ACh) is critical in controlling epithelial ion transport and hence water movements for gut hydration. Here we review the mechanism of cholinergic control of epithelial ion transport across the mammalian intestine. The cholinergic nervous system affects basal ion flux and can evoke increased active ion transport events. Most studies rely on measuring increases in short-circuit current (I SC ¼ active ion transport) evoked by adding ACh or cholinomimetics to intestinal tissue mounted in Ussing chambers. Despite subtle species and gut regional differences, most data indicate that, under normal circumstances, the effect of ACh on intestinal ion transport is mainly an increase in Cl -secretion due to interaction with epithelial M 3 muscarinic ACh receptors (mAChRs) and, to a lesser extent, neuronal M 1 mAChRs; however, AChR pharmacology has been plagued by a lack of good receptor subtype-selective compounds. Mice lacking M 3 mAChRs display intact cholinergically-mediated intestinal ion transport, suggesting a possible compensatory mechanism. Inflamed tissues often display perturbations in the enteric cholinergic system and reduced intestinal ion transport responses to cholinomimetics. The mechanism(s) underlying this hyporesponsiveness are not fully defined. Inflammation-evoked loss of mAChR-mediated control of epithelial ion transport in the mouse reveals a role for neuronal nicotinic AChRs, representing a hitherto unappreciated braking system to limit ACh-evoked Cl -secretion. We suggest that: i) pharmacological analyses should be supported by the use of more selective compounds and supplemented with molecular biology techniques targeting specific ACh receptors and signalling molecules, and ii) assessment of ion transport in normal tissue must be complemented with investigations of tissues from patients or animals with intestinal disease to reveal control mechanisms that may go undetected by focusing on healthy tissue only.

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Section: Cholinergic Control Of Enteric Epithelial Ion Transportmentioning

confidence: 99%

“…evidence that should caution against making broad conclusions based on individual studies: Prior et al (2004) showed that colonic tissue from two lines of the Flinders strain of rats have different TTX sensitivities to CCh-induced increases in I SC .…”

Section: Stimulated Ion Transportmentioning

confidence: 99%