Abstract
Transient receptor potential ankyrin1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1) are members of the TRP superfamily of structurally related, nonselective cation channels and mediators of several signaling pathways. Previously, we identified methyl syringate as an hTRPA1 agonist with efficacy against gastric emptying. The aim of this study was to find hTRPA1 and/or hTRPV1 activators in Agastache rugosa (Fisch. et Meyer) O. Kuntze (A.rugosa), commonly known as Korean mint to improve hTRPA1-related phenomena. An extract of the stem and leaves of A.rugosa (Labiatae) selectively activated hTRPA1 and hTRPV1. We next investigated the effects of commercially available compounds found in A.rugosa (acacetin, 4-allylanisole, p-anisaldehyde, apigenin 7-glucoside, L-carveol, β-caryophyllene, trans-p-methoxycinnamaldehyde, methyl eugenol, pachypodol, and rosmarinic acid) on cultured hTRPA1- and hTRPV1-expressing cells. Of the ten compounds, L-carveol, trans-p-methoxycinnamaldehyde, methyl eugenol, 4-allylanisole, and p-anisaldehyde selectively activated hTRPA1, with EC50 values of 189.1±26.8, 29.8±14.9, 160.2±21.9, 1535±315.7, and 546.5±73.0 μM, respectively. The activities of these compounds were effectively inhibited by the hTRPA1 antagonists, ruthenium red and HC-030031. Although the five active compounds showed weaker calcium responses than allyl isothiocyanate (EC50=7.2±1.4 μM), our results suggest that these compounds from the stem and leaves of A.rugosa are specific and selective agonists of hTRPA1.
Highlights
Transient receptor potential ankyrin1 (TRPA1), a member of the large TRP family of ion channels, is widely expressed in peripheral and sensory neurons [1,2,3]
The Ca2+ responses induced by allyl isothiocyanate (AITC) and the extract were inhibited by the general TRP channel blocker, ruthenium red (RR) (30 μM) and a selective TRPA1 blocker, HC-030031 (100 μM) in hTRPA1-Flp-In 293 stable cells, and by RR (30 μM) and CPZ (5 μM) in HEK293T cells transiently expressing hTRPV1
The cytosolic Ca2+ influxes induced by 4-allylanisole (1 mM), p-anisaldehyde (1 mM), L-carveol (300 μM), trans-p-methoxycinnamaldehyde (100 μM), and methyl eugenol (300 μM) in hTRPA1-Flp-In 293 stable cells were mostly blocked by 30 μM RR and 100 μM HC-030031 (Fig 3)
Summary
Transient receptor potential ankyrin (TRPA1), a member of the large TRP family of ion channels, is widely expressed in peripheral and sensory neurons [1,2,3]. Many cell types, tissues, and organs including enterochromaffin cells, airway epithelial cells, the brain, and hair cells, express TRPA1. TRPA1 is involved in diverse activities, including acute and chronic pain and inflammation, delayed gastric emptying, cold sensation (
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