Optical Control of Adenosine-Mediated Pain Modulation,Bioconjugate Chemistry

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Optical Control of Adenosine-Mediated Pain Modulation
Bioconjugate Chemistry ( IF 4.0 ) Pub Date : 2021-08-27 , DOI: 10.1021/acs.bioconjchem.1c00387
Katharina Hüll _{1,

2} , Víctor Fernández-Dueñas _{3,

4} , Matthias Schönberger ₂ , Marc López-Cano _{3,

4} , Dirk Trauner ₁ , Francisco Ciruela _{3,

4}

Affiliation

Adenosine receptors (ARs) play many important roles in physiology and have been recognized as potential targets for pain relief. Here, we introduce three photoswitchable adenosine derivatives that function as light-dependent agonists for ARs and confer optical control to these G protein-coupled receptors. One of our compounds, AzoAdenosine-3, was evaluated in the classical formalin model of pain. The molecule, active in the dark, was not metabolized by adenosine deaminase and effectively reduced pain perception in a light-dependent manner. These antinociceptive effects suggested a major role for A₁R and A₃R in peripheral-mediated pain sensitization, whereas an average adenosine-mediated antinociceptive effect will be facilitated by A_2AR and A_2BR. Our results demonstrate that a photoswitchable adenosine derivative can be used to map the contribution of ARs mediating analgesia in vivo.

中文翻译：

腺苷介导的疼痛调节的光学控制

腺苷受体（AR）在生理学中发挥着许多重要作用，并已被认为是缓解疼痛的潜在靶点。在这里，我们介绍了三种光开关腺苷衍生物，它们充当 AR 的光依赖性激动剂，并对这些 G 蛋白偶联受体赋予光学控制。我们的一种化合物 AzoAdenosine-3 在经典福尔马林疼痛模型中进行了评估。该分子在黑暗中活跃，不被腺苷脱氨酶代谢，并以光依赖性方式有效减少疼痛感知。这些抗伤害作用表明 A ₁ R 和 A ₃ R 在外周介导的疼痛敏化中起主要作用，而平均腺苷介导的抗伤害作用将由 A _2A R 和 A _2B R 促进。我们的结果表明，光可切换腺苷衍生物可用于绘制 AR 介导体内镇痛的贡献。

更新日期：2021-09-15

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