The physiological role of the adenosine A3 receptor is being investigated using newly synthesized, selective ligands. Recently, in addition to agonists, selective antagonists have been developed that belong to three distinct, non-purine chemical classes: flavonoids, 1,4-dihydropyridine derivatives (e.g. MRS1191, which is 1300-fold selective for human adenosine A3 vs A1/A2A receptors, with a Ki value of 31 nM) and the triazoloquinazolines (e.g. MRS1220, which has a Ki value of 0.65 nM). The A3 receptor has proven enigmatic in terms of antagonist ligand specificity, coupling to second messengers, and biological effects in the CNS, inflammatory system and cardiovascular system. A3 receptors are also potentially involved in apoptosis. It appears that intense, acute activation of A3 receptors acts as a lethal input to cells, while low concentrations of A3 receptor agonists protect against apoptosis. Here, Kenneth Jacobson describes how A3 receptor agonists might be useful in treating inflammatory conditions, possibly through their inhibition of tumour necrosis factor alpha (TNF-alpha) release, which has been shown in macrophages. A3 receptor antagonists might be useful in treating asthma or acute brain ischaemia. Recently, the versatility of A3 receptor agonists, administered either before or during ischaemia, in eliciting potent cardioprotection has been shown.

中文翻译：

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腺苷 A3 受体：新型配体和矛盾效应。


正在使用新合成的选择性配体研究腺苷 A3 受体的生理作用。最近，除了激动剂之外，还开发了属于三种不同的非嘌呤化学类别的选择性拮抗剂：类黄酮、1,4-二氢吡啶衍生物（例如MRS1191，其对人腺苷A3的选择性是A1/A2A的1300倍）受体（Ki 值为 31 nM）和三唑并喹唑啉（例如 MRS1220，Ki 值为 0.65 nM）。事实证明，A3 受体在拮抗剂配体特异性、与第二信使的偶联以及中枢神经系统、炎症系统和心血管系统中的生物效应方面具有神秘性。 A3 受体也可能参与细胞凋亡。似乎 A3 受体的强烈、急性激活对细胞起到致命的输入作用，而低浓度的 A3 受体激动剂可以防止细胞凋亡。在这里，Kenneth Jacobson 描述了 A3 受体激动剂如何在治疗炎症方面发挥作用，可能是通过抑制肿瘤坏死因子 α (TNF-α) 的释放，这一点已在巨噬细胞中得到证实。 A3 受体拮抗剂可能有助于治疗哮喘或急性脑缺血。最近，A3受体激动剂在缺血之前或期间施用，在引发有效的心脏保护方面已显示出多功能性。