Reference - Detail
|Author||Iwasaki Y, Tanabe M, Kayama Y, Abe M, Kashio M, Koizumi K, Okumura Y, Morimitsu Y, Tominaga M, Ozawa Y, Watanabe T.|
|Title||Miogadial and miogatrial with alpha,beta-unsaturated 1,4-dialdehyde moieties--novel and potent TRPA1 agonists.|
AIMS: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.
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.
|MeSH||Aldehydes / chemistry* Animals Behavior, Animal / drug effects CHO Cells Calcium / metabolism Cell Line Cricetinae Cricetulus Diterpenes / chemistry* Diterpenes / pharmacology* Electrophysiology Ganglia, Spinal / cytology Ganglia, Spinal / drug effects Humans Male Mice Mice, Inbred C57BL Pain / psychology Sensory Receptor Cells / drug effects Sesquiterpenes / pharmacology Structure-Activity Relationship TRPA1 Cation Channel TRPV Cation Channels / agonists Transient Receptor Potential Channels / agonists*|
|WOS Category||PHARMACOLOGY & PHARMACY MEDICINE, RESEARCH & EXPERIMENTAL|
|Human and Animal Cells|