SANKEN, Osaka University, Ibaraki, Osaka, Japan.
Graduate School of Frontier Biosciences, Osaka University, Suita, Osaka, Japan.
Biosci Biotechnol Biochem. 2024 Oct 22;88(11):1316-1325. doi: 10.1093/bbb/zbae119.
Vanilloid analogs, which can activate transient receptor potential vanilloid 1 (TRPV1), have been classified into two types based on susceptibility to forskolin (FSK). Treatment of cells expressing TRPV1 with FSK enhances TRPV1 responses to capsaicin-type ligands while diminishing the responses to eugenol-type ligands. In this study, we determined the effect of FSK on the activation of TRPV1 stimulated with vanilloid ligands, through the influx of Ca2+ in HEK293T cells expressing TRPV1. Our findings suggest that the effects of FSK can be attributed to the phosphorylation of TRPV1, as evidenced by using a protein kinase A inhibitor and TRPV1 mutants at potential phosphorylation sites. Furthermore, we examined the structure-activity relationship of 13 vanilloid analogs. Our results indicated that vanilloid compounds could be classified into three types, that is the previously reported two types and a novel type of 10-shogaol, by which TRPV1 activation was insusceptible to the FSK treatment.
香草醛类似物可激活瞬时受体电位香草醛 1 (TRPV1)，根据对 forskolin (FSK) 的敏感性可将其分为两类。用 FSK 处理表达 TRPV1 的细胞可增强 TRPV1 对辣椒素型配体的反应，同时降低对丁香酚型配体的反应。在这项研究中，我们通过测定 TRPV1 表达的 HEK293T 细胞中 Ca2+ 的内流，确定了 FSK 对香草醛配体刺激的 TRPV1 激活的影响。我们的发现表明，FSK 的作用可归因于 TRPV1 的磷酸化，这可通过使用蛋白激酶 A 抑制剂和 TRPV1 潜在磷酸化位点的突变体来证明。此外，我们还研究了 13 种香草醛类似物的构效关系。结果表明，根据 TRPV1 激活对 FSK 处理的敏感性，香草醛化合物可分为三类，即先前报道的两类和一种新型的 10-姜烯酚。
