The TRPA1 Agonist Cinnamaldehyde Induces the Secretion of HCO3- 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 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.
['Manneck|David|D|0000-0003-4478-1980', 'Manz|Gisela|G|', 'Braun|Hannah-Sophie|HS|', 'Rosendahl|Julia|J|', 'Stumpff|Friederike|F|0000-0001-9518-9237']
D000171:Acrolein D000818:Animals D000972:Antineoplastic Agents, Phytogenic D001639:Bicarbonates D004847:Epithelial Cells D041981:Gastrointestinal Tract D013552:Swine D000074025:TRPA1 Cation Channel
TRPA1 cinnamaldehyde colon Ussing chamber TRPV3 patch clamp prostaglandin colonic buffering epithelial transport essential oils intestine pig