Miogadial and miogatrial with α,β-unsaturated 1,4-dialdehyde moieties—Novel and potent TRPA1 agonists

Life Sci 85(1-2):60-69 (2009) PMID 19409911

Aims: Most of the terpenoids with an @a,@b-unsaturated 1,4-dialdehyde moiety, which are found in plants, fungi, and insects, have a pungent taste. However, the neural receptors responsible for the pungency of these terpenoids have not been identified yet. The transient receptor potential ankyrin 1 (TRPA1) and transient receptor potential vanilloid 1 (TRPV1), which are expressed in the nociceptive neurons, induce a sensation of heat on activation by some pungent ingredients in food. In this study, we selected miogadial (MD), miogatrial (MT), and polygodial (PG) from the terpenoids with an @a,@b-unsaturated 1,4-dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or TRPV1. Main methods: TRPV1 and TRPA1 activity by 3 terpenoids were evaluated using Ca^2^+ imaging and patch-clamp methods in mammalian cells that express TRP heterologously and mouse sensory neurons. Key findings: The 3 terpenoids activated TRPA1 that was heterologously expressed in HEK293 or CHO cells. The potencies of activation by the 3 terpenoids were equal and almost 10 times stronger than that of allyl isothiocyanate (AITC), which is known as the most potent TRPA1 agonist among all natural products. Moreover, these 3 terpenoids exhibited increased intracellular Ca^2^+ concentration in mouse sensory neuron cells compared to AITC. High concentrations of the 3 terpenoids also activated TRPV1 that was heterologously expressed in HEK293 cells. Significance: These results indicated that MD, MT, and PG were more potent in activating TRPA1 than TRPV1, and suggested that they primarily activate TRPA1 to induce pungency.

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