The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon
A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing...
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MDPI AG
2021-05-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/10/5198 |
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| author | David Manneck Gisela Manz Hannah-Sophie Braun Julia Rosendahl Friederike Stumpff |
| author_facet | David Manneck Gisela Manz Hannah-Sophie Braun Julia Rosendahl Friederike Stumpff |
| author_sort | David Manneck |
| collection | DOAJ |
| description | A therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·L<sup>−1</sup> cinnamaldehyde induced increases in short circuit current (ΔI<sub>sc</sub>) and conductance (ΔG<sub>t</sub>) across the colon that were higher than those across the jejunum or after 1 mmol·L<sup>−1</sup> thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L<sup>−1</sup> quinidine or the bilateral replacement of 120 Na<sup>+</sup>, 120 Cl<sup>−</sup> or 25 HCO<sub>3</sub><sup>−</sup> reduced ΔG<sub>t</sub>, while the removal of Ca<sup>2+</sup> enhanced ΔG<sub>t</sub> with ΔI<sub>sc</sub> numerically higher. ΔI<sub>sc</sub> decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na<sup>+</sup> or 25 HCO<sub>3</sub><sup>−</sup>. The removal of 120 Cl<sup>−</sup> had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO<sub>3</sub><sup>−</sup> via apical CFTR and basolateral Na<sup>+</sup>-HCO<sub>3</sub><sup>−</sup> cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1. |
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| issn | 1661-6596 1422-0067 |
| language | English |
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| spelling | doaj.art-e91a5c57a8024992b12513c3e889669f2023-11-21T19:43:38ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-05-012210519810.3390/ijms22105198The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine ColonDavid Manneck0Gisela Manz1Hannah-Sophie Braun2Julia Rosendahl3Friederike Stumpff4Department of Veterinary Medicine, Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, GermanyDepartment of Veterinary Medicine, Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, GermanyPerformaNat GmbH, Hohentwielsteig 6, 14163 Berlin, GermanyPerformaNat GmbH, Hohentwielsteig 6, 14163 Berlin, GermanyDepartment of Veterinary Medicine, Institute of Veterinary Physiology, Freie Universität Berlin, Oertzenweg 19b, 14163 Berlin, GermanyA therapeutic potential of the TRPA1 channel agonist cinnamaldehyde for use in inflammatory bowel disease is emerging, but the mechanisms are unclear. Semi-quantitative qPCR of various parts of the porcine gastrointestinal tract showed that mRNA for TRPA1 was highest in the colonic mucosa. In Ussing chambers, 1 mmol·L<sup>−1</sup> cinnamaldehyde induced increases in short circuit current (ΔI<sub>sc</sub>) and conductance (ΔG<sub>t</sub>) across the colon that were higher than those across the jejunum or after 1 mmol·L<sup>−1</sup> thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L<sup>−1</sup> quinidine or the bilateral replacement of 120 Na<sup>+</sup>, 120 Cl<sup>−</sup> or 25 HCO<sub>3</sub><sup>−</sup> reduced ΔG<sub>t</sub>, while the removal of Ca<sup>2+</sup> enhanced ΔG<sub>t</sub> with ΔI<sub>sc</sub> numerically higher. ΔI<sub>sc</sub> decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na<sup>+</sup> or 25 HCO<sub>3</sub><sup>−</sup>. The removal of 120 Cl<sup>−</sup> had no effect. Cinnamaldehyde also activates TRPV3, but comparative measurements involving patch clamp experiments on overexpressing cells demonstrated that much higher concentrations are required. We suggest that cinnamaldehyde stimulates the secretion of HCO<sub>3</sub><sup>−</sup> via apical CFTR and basolateral Na<sup>+</sup>-HCO<sub>3</sub><sup>−</sup> cotransport, preventing acidosis and damage to the epithelium and the colonic microbiome. Signaling may involve the opening of TRPA1, depolarization of the epithelium and a rise in PGE2 following a lower uptake of prostaglandins via OATP2A1.https://www.mdpi.com/1422-0067/22/10/5198cinnamaldehydecoloncolonic bufferingepithelial transportessential oilsintestine |
| spellingShingle | David Manneck Gisela Manz Hannah-Sophie Braun Julia Rosendahl Friederike Stumpff The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon International Journal of Molecular Sciences cinnamaldehyde colon colonic buffering epithelial transport essential oils intestine |
| title | The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon |
| title_full | The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon |
| title_fullStr | The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon |
| title_full_unstemmed | The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon |
| title_short | The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO<sub>3</sub><sup>−</sup> by the Porcine Colon |
| title_sort | trpa1 agonist cinnamaldehyde induces the secretion of hco sub 3 sub sup sup by the porcine colon |
| topic | cinnamaldehyde colon colonic buffering epithelial transport essential oils intestine |
| url | https://www.mdpi.com/1422-0067/22/10/5198 |
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