Journal article

Publication year: 2016

Pages: 2766-2779

Journal: British Journal of Pharmacology

Volume number: 173

Issue number: 18

ISSN: 0007-1188

Open access status: Green

DOI Link: https://doi.org/10.1111/bph.13555

Publisher: Wiley

Abstract: 
Background and PurposeThe colonic surface epithelium produces acetylcholine, released after the binding of propionate to GPCRs for this short-chain fatty acid (SCFA). This epithelial acetylcholine then induces anion secretion via stimulation of acetylcholine receptors. The key enzyme responsible for acetylcholine synthesis, choline acetyltransferase, is known to be unselective as regards the fatty acid used for esterification of choline. As the colonic epithelium is permanently exposed to high concentrations of different SCFAs produced by bacterial fermentation, we investigated whether choline esters other than acetylcholine, propionylcholine and butyrylcholine, are produced by the colonic epithelium, too, and whether these atypical' esters are able to stimulate the acetylcholine receptors involved in the regulation of colonic ion transport.Experimental ApproachDesorption electrospray ionization mass spectroscopy (DESI-MS), Ussing chamber and Ca2+-imaging experiments were performed on rat distal colon.Key ResultsDESI-MS analyses revealed the production of acetylcholine, propionylcholine and butyrylcholine in the surface epithelium. Relative expression rates were 2-3% in comparison with acetylcholine. In Ussing chamber experiments, both atypical choline esters caused a concentration-dependent increase in short-circuit current, that is, stimulated anion secretion. Inhibitor experiments in the absence and presence of the submucosal plexus revealed the involvement of neuronal and epithelial acetylcholine receptors. While butyrylcholine obviously stimulated both nicotinic and muscarinic receptors, propionylcholine predominantly acted on muscarinic receptors.Conclusions and ImplicationsThese results suggest a novel pathway for communication between intestinal microbes producing SCFA and the host via modification of epithelial production of choline esters involved in the paracrine regulation of the colonic epithelium.

Harvard Citation style: Moreno, S., Gerbig, S., Schulz, S., Spengler, B., Diener, M. and Bader, S. (2016) Epithelial propionyl- and butyrylcholine as novel regulators of colonic ion transport, British Journal of Pharmacology, 173(18), pp. 2766-2779. https://doi.org/10.1111/bph.13555

APA Citation style: Moreno, S., Gerbig, S., Schulz, S., Spengler, B., Diener, M., & Bader, S. (2016). Epithelial propionyl- and butyrylcholine as novel regulators of colonic ion transport. British Journal of Pharmacology. 173(18), 2766-2779. https://doi.org/10.1111/bph.13555