School of Food Science and Engineering, Qilu University of Technology (Shandong Academy of Sciences), No. 3501 University Road of Changqing District, Jinan, 250353, Shandong Province, China.
Shandong Women's University, No. 2399 University Road of Changqing District, Jinan, 250300, Shandong Province, China.
J Mol Neurosci. 2018 Oct;66(2):207-213. doi: 10.1007/s12031-018-1156-5. Epub 2018 Aug 17.
The activity of sweet taste receptor (heterodimeric T1R2 and T1R3) can be modulated by sweet regulators. The compound amiloride can inhibit the sweet sensitivity of the human sweet taste receptor. This study describes the species-dependent regulation of the response of sweet taste receptors by this sweet inhibitor. Amiloride inhibited the sweet taste response of humans and mice but not that of squirrel monkeys. Using human/squirrel monkey/mouse chimeric T1R2 and T1R3 receptors as well as the agonist perillartine (which can activate the single heptahelical domain of T1R2), we found that the heptahelical domain of T1R2 is the molecular determinant that mediates the species-dependent sensitivity to this sweet regulator. Compared to the sweet inhibitor lactisole (which acts on T1R3), amiloride has a different allosteric binding site on the sweet receptor, which is important new information for the design of novel sweet taste modulators that act on T1R2.
甜味受体（异二聚体 T1R2 和 T1R3）的活性可以被甜味调节剂调节。化合物阿米洛利可以抑制人甜味受体的甜味敏感性。本研究描述了这种甜味抑制剂对不同物种甜味受体反应的调节作用。阿米洛利抑制了人类和小鼠的甜味反应，但对松鼠猴的甜味反应没有抑制作用。使用人/松鼠猴/鼠嵌合 T1R2 和 T1R3 受体以及激动剂紫苏醇（可以激活 T1R2 的单个七螺旋域），我们发现 T1R2 的七螺旋域是介导对这种甜味调节剂的物种依赖性敏感性的分子决定因素。与作用于 T1R3 的甜味抑制剂乳果糖相比，阿米洛利在甜味受体上具有不同的变构结合位点，这为设计作用于 T1R2 的新型甜味调节剂提供了重要的新信息。
