Journal article

Publication year: 2021

Journal: European Journal of Pharmacology

Volume number: 906

ISSN: 0014-2999

eISSN: 1879-0712

DOI Link: https://doi.org/10.1016/j.ejphar.2021.174292

Publisher: Elsevier

Abstract: 
Short-chain fatty acids (SCFAs) produced by the microbial fermentation of carbohydrates are important energy substrates for mammals. Intestinal epithelia respond to these metabolites by stimulation of anion secretion via the release of epithelial acetylcholine. The present experiments were performed to discover which of the known receptors for SCFAs are expressed in rat caecum, the most important site of fermentation within the intestine of non-ruminant mammals. Using the increase in short-circuit current (Isc) induced by anion secretion as the readout, the order of efficiency of the tested SCFAs in rat caecum was propionate > butyrate > acetate. Both synthetic high-affinity selective free fatty acid (FFA) receptor agonists 4-CMTB (FFA2 receptor) and AR420626 (FFA3 receptor) partially mimicked the effect of propionate on Isc (IProp). IProp was concentration-dependently inhibited by the FFA3 receptor antagonist beta-OH-butyrate. Although no antagonist of rat FFA2 receptor is available, coadministration of the allosteric FFA2 receptor agonist 4-CMTB together with a low concentration of propionate potentiated IProp, suggesting that FFA2 receptor is involved in sensing of short-chain fatty acids as well. The expression of both receptor types was confirmed by qPCR (with FFA2 > FFA3 receptor). Immunohistochemical staining revealed the localization of FFA2 receptor in the surface epithelium and the FFA3 receptor expression predominantly in enteroendocrine cells and subepithelial nerve-like fibers. Taken together, the present results demonstrate that the anion secretion induced by the microbial metabolite propionate in rat caecum is enhanced by activation of FFA2 and FFA3 receptor expressed in different cell types within the caecal epithelium.

Harvard Citation style: Ballout, J., Akiba, Y., Kaunitz, J. and Diener, M. (2021) Short-chain fatty acid receptors involved in epithelial acetylcholine release in rat caecum, European Journal of Pharmacology, 906, Article 174292. https://doi.org/10.1016/j.ejphar.2021.174292

APA Citation style: Ballout, J., Akiba, Y., Kaunitz, J., & Diener, M. (2021). Short-chain fatty acid receptors involved in epithelial acetylcholine release in rat caecum. European Journal of Pharmacology. 906, Article 174292. https://doi.org/10.1016/j.ejphar.2021.174292