Kawasaki Maiko, Kidera Yuta, Goda Ryusei, Taketani Chiaki, Ide Misato, Fujii Wataru, Nakagita Tomoya, Misaka Takumi
Department of Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, 1-1-1 Yayoi, Bunkyo-ku, Tokyo, 113-8657, Japan.
Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, 113-8657, Japan.
Sci Rep. 2025 Jul 25;15(1):27167. doi: 10.1038/s41598-025-11636-0.
The heterodimeric G-protein-coupled receptors T1R2/T1R3 and T1R1/T1R3 have been identified as sweet and umami taste receptors, respectively, and both of these receptors share the T1R3 subunit. Previous research has indirectly indicated functional differences in the T1R3 subunit between the receptors. In this study, a comparative analysis was conducted on the responses of these receptors to substances acting on T1R3, standardizing the response measurement conditions for both. The results revealed significant differences in the modulatory effects of negative allosteric modulators (NAMs) and positive allosteric modulators (PAMs), that act on the transmembrane region of T1R3. Notably, (±)-lactisole, (±)-2,4-DP, and clofibric acid, which are sweet taste receptor inhibitors, also function as umami taste receptor inhibitors, albeit at concentrations approximately 6-10 times greater than those required for sweet taste inhibition. Additionally, cyclamate and NHDC, which are ago-PAMs of sweet taste receptors, did not activate the umami taste receptor at any concentration that significantly elicited sweet taste receptor responses. These results suggest that the binding modes of the substances to the T1R3 subunit of the sweet taste receptor and umami taste receptor are not entirely identical. The difference in the heterodimeric partners to T1R3 may account for their distinct modulation patterns of receptor function.
异二聚体G蛋白偶联受体T1R2/T1R3和T1R1/T1R3已分别被鉴定为甜味和鲜味味觉受体，且这两种受体都共享T1R3亚基。先前的研究已间接表明这两种受体的T1R3亚基存在功能差异。在本研究中，对这些受体对作用于T1R3的物质的反应进行了比较分析，同时对两者的反应测量条件进行了标准化。结果显示，作用于T1R3跨膜区域的负变构调节剂（NAMs）和正变构调节剂（PAMs）的调节作用存在显著差异。值得注意的是，甜味受体抑制剂（±）-乳酰苯并噻唑、（±）-2,4-二磷酸和氯贝酸也可作为鲜味受体抑制剂，尽管其浓度比抑制甜味所需的浓度高约6至10倍。此外，甜味受体的前体PAMs甜蜜素和NHDC在任何能显著引发甜味受体反应的浓度下均未激活鲜味受体。这些结果表明，这些物质与甜味受体和鲜味受体的T1R3亚基的结合模式并不完全相同。T1R3异二聚体伴侣的差异可能解释了它们不同的受体功能调节模式。
