Miogadial and miogatrial with alpha,beta-unsaturated 1,4-dialdehyde moieties--novel and potent TRPA1 agonists.
OBJECTIVE
Most of the terpenoids with an alpha,beta-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 alpha,beta-unsaturated 1,4-dialdehyde moiety and examined the effects of these 3 terpenoids on TRPA1 or TRPV1.


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.


RESULTS
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.


CONCLUSIONS
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.
Iwasaki
Yusaku
Y
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.
Tanabe
Manabu
M
Kayama
Yuko
Y
Abe
Masako
M
Kashio
Makiko
M
Koizumi
Kanako
K
Okumura
Yukiko
Y
Morimitsu
Yasujiro
Y
Tominaga
Makoto
M
Ozawa
Yoshio
Y
Watanabe
Tatsuo
T
D000447:Aldehydes / Q000737:chemistry*; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D016466:CHO Cells; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D006224:Cricetinae; D003412:Cricetulus; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D004594:Electrophysiology; D005727:Ganglia, Spinal / Q000166:cytology / Q000187:drug effects; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010146:Pain / Q000523:psychology; D011984:Sensory Receptor Cells / Q000187:drug effects; D012717:Sesquiterpenes / Q000494:pharmacology; D013329:Structure-Activity Relationship; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels / Q000819:agonists; D050051:Transient Receptor Potential Channels / Q000819:agonists*
C541794:12-labdene-15,16,(8)17-trial; D000447:Aldehydes; D004224:Diterpenes; D012717:Sesquiterpenes; D000074025:TRPA1 Cation Channel; D050916:TRPV Cation Channels; C493921:TRPV1 protein, mouse; D050051:Transient Receptor Potential Channels; C475685:Trpa1 protein, mouse; C476263:miogadial; C034380:polygodial; D002118:Calcium