TRPA1 causes rapid bronchodilation via non-epithelial PGE2.

TRPA1 causes rapid bronchodilation via non-epithelial PGE2. Am J Physiol Lung Cell Mol Physiol. 2020 Apr 01;: Authors: Marsh BJ, Fryer AD, Jacoby DB, Drake MG Abstract Transient Potential Receptor Ankyrin 1 (TRPA1) is a ligand-gated cation channel that responds to endogenous and exogenous irritants. TRPA1 is expressed on multiple cell types throughout the lungs, but previous studies have primarily focused on TRPA1 stimulation of airway sensory nerves. We sought to understand the integrated physiologic airway response to TRPA1 stimulation. The TRPA1 agonists allyl isothiocyanate (AITC) and cinnamaldehyde (CINN) were tested in sedated, mechanically ventilated guinea pigs in vivo. Reproducible bronchoconstrictions were induced by electrical stimulation of the vagus nerves. Animals were then treated with intravenous AITC or CINN. AITC and CINN were also tested on isolated guinea pig and mouse tracheas, and post- mortem human trachealis muscle strips in an organ bath. Tissues were contracted with methacholine, histamine, or potassium chloride, then treated with AITC or CINN. Some airways were pre-treated with TRPA1 antagonists, the cyclooxygenase inhibitor indomethacin, the EP2 receptor antagonist PF04418948, or tetrodotoxin. AITC and CINN blocked vagally-mediated bronchoconstriction in guinea pigs. Pretreatment with indomethacin completely abolished the airway response to TRPA1 agonists. Similarly, AITC and CINN dose-dependently relaxed ...
Source: American Journal of Physiology. Lung Cellular and Molecular Physiology - Category: Cytology Authors: Tags: Am J Physiol Lung Cell Mol Physiol Source Type: research