Abstract
Transient receptor potential ankyrin 1 (TRPA1) is a calcium-permeable non-selective cation channel that is activated by various noxious or irritant substances in nature, including spicy compounds. Many TRPA1 chemical activators have been reported; however, only limited information is available regarding the amino acid residues that contribute to the activation by non-electrophilic activators, whereas activation mechanisms by electrophilic ligands have been well characterized. We used intracellular Ca(2+) measurements and whole-cell patch clamp recordings to show that eudesmol, an oxygenated sesquiterpene present at high concentrations in the essential oil of hop cultivar Hallertau Hersbrucker, could activate human TRPA1. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. This activation was completely blocked by a TRPA1-specific inhibitor, HC03-0031. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely threonine at 813, tyrosine at 840, and serine at 873, for activation by β-eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil and provide a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals.
Highlights
Transient receptor potential ankyrin 1 (TRPA1) is activated by many spicy compounds by unknown mechanisms
Eudesmol Is a Characteristic Oxygenated Sesquiterpenoid Found in the Hop Cones of Cultivar Hallertau Hersbrucker— The characteristic spicy taste from hop cones of cultivar HHE is reported to be due to oxygenated sesquiterpenoid [15]
Empirical sensory assessments have evaluated that HHE produces a spicy character in beer [14]; our results of human TRPA1 (hTRPA1) activation by eudesmol could help explain these sensory phenomena
Summary
Transient receptor potential ankyrin 1 (TRPA1) is activated by many spicy compounds by unknown mechanisms. Results: The amino acids critical for the activation of TRPA1 by the hop-derived sesquiterpene -eudesmol were identified. Transient receptor potential ankyrin 1 (TRPA1) is a calciumpermeable non-selective cation channel that is activated by various noxious or irritant substances in nature, including spicy compounds. Gradual activation of inward currents with outward rectification by eudesmol was observed in human embryonic kidney-derived 293 cells expressing human TRPA1. We identified three critical amino acid residues in human TRPA1 in putative transmembrane domains 3, 4, and 5, namely threonine at 813, tyrosine at 840, and serine at 873, for activation by -eudesmol in a systematic mutational study. Our results revealed a new TRPA1 activator in hop essential oil and provide a novel insight into mechanisms of human TRPA1 activation by non-electrophilic chemicals.
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