title: Epithelial propionyl- and butyrylcholine as novel regulators of colonic ion transport.
abstract: The 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.
  
  
  
  Desorption electrospray ionization mass spectroscopy (DESI-MS), Ussing chamber and Ca(2+) -imaging experiments were performed on rat distal colon.
  
  
  
  DESI-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.
  
  
  
  These 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.
authors.affiliation: Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen.
authors.forename: Sarah
authors.initials: S
authors.lastname: Moreno
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University Giessen.
authors.forename: Stefanie
authors.initials: S
authors.lastname: Gerbig
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University Giessen.
authors.forename: Sabine
authors.initials: S
authors.lastname: Schulz
authors.affiliation: Institute of Inorganic and Analytical Chemistry, Justus-Liebig-University Giessen.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Spengler
authors.affiliation: Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen.
authors.forename: Martin
authors.identifier: 0000-0003-2194-4636
authors.initials: M
authors.lastname: Diener
authors.affiliation: Institute of Veterinary Physiology and Biochemistry, Justus-Liebig-University Giessen.
authors.forename: Sandra
authors.initials: S
authors.lastname: Bader
mesh_terms: D000818:Animals; D002794:Choline / Q000031:analogs & derivatives* / Q000096:biosynthesis / Q000494:pharmacology; D003106:Colon / Q000187:drug effects* / Q000378:metabolism; D004847:Epithelial Cells / Q000737:chemistry* / Q000378:metabolism; D005260:Female; D017136:Ion Transport / Q000187:drug effects; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: C017100:butyrylcholine; C009062:propionylcholine; D002794:Choline