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：

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腺苷介导的疼痛调制的光学控制

腺苷受体 (AR) 在生理学中发挥着许多重要作用，并且已被公认为缓解疼痛的潜在目标。在这里，我们介绍了三种光控腺苷衍生物，它们作为 AR 的光依赖性激动剂，并赋予这些 G 蛋白偶联受体光学控制。我们的一种化合物 AzoAdenosine-3 在经典的福尔马林疼痛模型中进行了评估。该分子在黑暗中活跃，不会被腺苷脱氨酶代谢，并以光依赖的方式有效降低疼痛感。这些镇痛作用表明 A ₁ R 和 A ₃ R 在外周介导的疼痛敏化中起主要作用，而 A _2A R 和 A _2B将促进平均腺苷介导的镇痛作用R. 我们的结果表明，可光控腺苷衍生物可用于绘制 ARs在体内介导镇痛的贡献。