ABSTRACT
In this study, we investigated the activation of TRPV1 and TRPA1 by N-acyl homoserine lactones, quorum sensing molecules produced by Gram-negative bacteria, and the inhibitory effect of TRPV1 and TRPA1 by autoinducing peptides (AIPs), quorum sensing molecules produced by Gram-positive bacteria, using human embryonic kidney 293T cell lines stably expressing human TRPV1 and TRPA1, respectively. As a result, we found that some N-acyl homoserine lactones, such as N-octanoyl-L-homoserine lactone (C8-HSL), N-nonanoyl-L-homoserine lactone (C9-HSL) and N-decanoyl-L-homoserine lactone (C10-HSL), activated both TRPV1 and TRPA1. In addition, we clarified that some N-acyl homoserine lactones, such as N-3-oxo-dodecanoyl-L-homoserine lactone (3-oxo-C12-HSL), only activated TRPV1 and N-acyl homoserine lactones having saturated short acyl chain, such as N-acetyl-L-homoserine lactone (C2-HSL) and N-butyryl-L-homoserine lactone (C4-HSL), only activated TRPA1. Furthermore, we found that an AIP, simple linear peptide CHWPR, inhibited both TRPV1 and TRPA1 and peptide having thiolactone ring DICNAYF, the thiolactone ring were formed between C3 to F7, strongly inhibited only the TRPV1. Although the specificity of TRPV1 and TRPA1 for quorum sensing molecules was different, these data suggest that both TRPV1 and TRPA1 would function as receptors for quorum sensing molecule produced by bacteria. Graphical Abstract.
Subject(s)
Acyl-Butyrolactones/pharmacology , Gram-Negative Bacteria/chemistry , Quorum Sensing , TRPA1 Cation Channel/metabolism , TRPV Cation Channels/metabolism , Acyl-Butyrolactones/chemistry , Gram-Negative Bacteria/genetics , Gram-Negative Bacteria/metabolism , HEK293 Cells , Humans , TRPA1 Cation Channel/chemistry , TRPA1 Cation Channel/genetics , TRPV Cation Channels/chemistry , TRPV Cation Channels/geneticsABSTRACT
In this study, we investigated the activation of Transient receptor potential vanilloid subtype 1, TRPV1, by lactones, a representative flavor ingredient currently used for foods and beverages. As a result, we found that some lactones having C4 acyl chain length, γ-octalactone, δ-nonalactone and ß-methyl-γ-octalactone, γ-undecalactone with C7 acyl chain length and δ-undecalactone with C6 acyl chain length activated TRPV1. TRPV1 is known as a non-selective cation channels that respond to a wide range of physical and chemical stimuli such as high temperature, protons, capsaicin and so on. Furthermore, it has been also demonstrated that activation of TRPV1 induced energy expenditure enhancement and thermogenesis, suppressed accumulation of visceral fat in mice and prevented non-alcoholic fatty acid liver. Thus, lactones that function as TRPV1 agonists are thought to be important candidates for decreasing the risks of developing a metabolic syndrome.
