Iwasaki Yusaku, Tanabe Manabu, Kayama Yuko, Abe Masako, Kashio Makiko, Koizumi Kanako, Okumura Yukiko, Morimitsu Yasujiro, Tominaga Makoto, Ozawa Yoshio, Watanabe Tatsuo
Graduate School of Nutritional and Environmental Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, Japan.
Life Sci. 2009 Jul 3;85(1-2):60-9. doi: 10.1016/j.lfs.2009.04.017. Epub 2009 May 3.
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.
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.
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.
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.
在植物、真菌和昆虫中发现的大多数具有α,β-不饱和1,4-二醛部分的萜类化合物都有刺鼻的味道。然而,负责这些萜类化合物刺鼻味道的神经受体尚未被鉴定出来。瞬时受体电位锚蛋白1(TRPA1)和瞬时受体电位香草酸亚型1(TRPV1)在伤害性神经元中表达,在被食物中的一些刺激性成分激活时会引起热感。在本研究中,我们从具有α,β-不饱和1,4-二醛部分的萜类化合物中选择了米奥加地尔(MD)、米奥加特里尔(MT)和聚癸二醛(PG),并研究了这3种萜类化合物对TRPA1或TRPV1的影响。
使用Ca(2+)成像和膜片钳方法,在异源表达TRP的哺乳动物细胞和小鼠感觉神经元中评估3种萜类化合物对TRPV1和TRPA1活性的影响。
这3种萜类化合物激活了在HEK293或CHO细胞中异源表达的TRPA1。这3种萜类化合物的激活效力相当,几乎比异硫氰酸烯丙酯(AITC)强10倍,而异硫氰酸烯丙酯是所有天然产物中最有效的TRPA1激动剂。此外,与AITC相比,这3种萜类化合物在小鼠感觉神经元细胞中使细胞内Ca(2+)浓度升高。高浓度的这3种萜类化合物也激活了在HEK293细胞中异源表达的TRPV1。
这些结果表明,MD、MT和PG在激活TRPA1方面比TRPV1更有效,并表明它们主要通过激活TRPA1来产生刺鼻味道。