Receptor mechanisms mediating activation of esophageal nerves by acid

Czech version

Authors: P. Bánovčin Jr; Martin Ďuriček; R. Hyrdel
Authors‘ workplace: Interná klinika gastroenterologická JLF UK a UN Martin, Slovenská republika
Published in: Gastroent Hepatol 2017; 71(1): 53-57
Category: Clinical and Experimental Gastroenterology: Review Article
doi: https://doi.org/10.14735/amgh201753

Overview

The pH in the esophageal lumen can be very low (pH 1) during acidic reflux. However, the pH in the esophageal mucosa where the esophageal afferent nerves terminate is predicted to be much higher (pH 5.5– 6.5). This is because the esophageal mucosal barrier, even when reduced in gastroesophageal reflux disease, still prevents most acid from diffusing into the esophageal tissue and causing widespread cellular death. It has therefore been predicted that the esophageal nociceptive (pain- and heartburn-mediating) nerves are stimulated by modest acid (pH 5.5–6.5) and express highly sensitive acid receptors. Recent studies in a guinea pig model demonstrated that weak acid (pH 5.5– 6.5) robustly stimulates esophageal spinal nociceptive C-fibers. Consistent with this observation, gene expression analysis revealed that esophageal C-fibers redundantly express multiple acid sensing ion channels (ASICs), proton-sensing G-protein coupled receptor OGR1, and the highly acid sensitive two-pore-domain (K2P) TASK1-family potassium channel. The high acid sensitivity of esophageal nociceptive nerves contributes to heartburn and pain in conditions of reduced mucosal barrier function (e. g. GERD), suggesting that the receptors mediating this high acid sensitivity could be targeted by novel drugs as a combinatorial therapy with, or an alternative to acid suppression.

Key words:
esophagus – gastroesophageal reflux disease – GERD – heartburn – acid sensing ion channel

The authors declare they have no potential conflicts of interest concerning drugs, products, or services used in the study.

The Editorial Board declares that the manuscrip met the ICMJE „uniform requirements“ for biomedical papers.

Submitted:
20. 8. 2015

Accepted:
3. 10. 2016

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