The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3- by the Porcine Colon.

David Manneck,Gisela Manz,Hannah-Sophie Braun,Friederike Stumpff,Julia Rosendahl

doi:10.3390/ijms22105198

Abstract

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−1 cinnamaldehyde induced increases in short circuit current (ΔIsc) and conductance (ΔGt) across the colon that were higher than those across the jejunum or after 1 mmol·L−1 thymol. Lidocaine, amiloride or bumetanide did not change the response. The application of 1 mmol·L−1 quinidine or the bilateral replacement of 120 Na+, 120 Cl− or 25 HCO3− reduced ΔGt, while the removal of Ca2+ enhanced ΔGt with ΔIsc numerically higher. ΔIsc decreased after 0.5 NPPB, 0.01 indometacin and the bilateral replacement of 120 Na+ or 25 HCO3−. The removal of 120 Cl− 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 HCO3− via apical CFTR and basolateral Na+-HCO3− 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.

Highlights

The transient receptor potential ankyrin channel (TRPA1) is a non-selective member of the large family of transient receptor potential (TRP) channels that is expressed by sensory neurons, epithelia and a wide variety of other cells, where it plays a key role as a sensor of multiple external and internal stimuli
RT-qPCR was used to investigate the relative amounts of mRNA encoding for TRPA1 in the gastrointestinal tissues of stomach, duodenum, jejunum, ileum, caecum, and colon of four pigs
Messenger RNA encoding for TRPA1 could be detected in all of the gastrointestinal epithelia investigated except for the ileum

Summary

Introduction

The transient receptor potential ankyrin channel (TRPA1) is a non-selective member of the large family of transient receptor potential (TRP) channels that is expressed by sensory neurons, epithelia and a wide variety of other cells, where it plays a key role as a sensor of multiple external and internal stimuli. In comparison to most other members of the TRP channel family, TRPA1 has a fairly high permeability to Ca2+ , with P(Na+ )/P(Ca2+ ) ~ 6, a value that can rise to about nine when the channel is opened by an agonist [1]. TRPA1 is a sensor for hyper- and hypoxia, various reactive oxygen species (ROS), H2 S, certain prostaglandins and an immense number of other chemical species and endogenous signals, many of which are associated with cell damage, and are

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