Molecular Recognition Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, MD 20892, USA.
Diabetes, Endocrinology and Obesity Branch, National Institute of Diabetes and Digestive and Kidney Diseases, NIH, Bethesda, MD 20892, USA.
Cells. 2020 Apr 13;9(4):956. doi: 10.3390/cells9040956.
Many ligands directly target adenosine receptors (ARs). Here we review the effects of noncanonical AR drugs on adenosinergic signaling. Non-AR mechanisms include raising adenosine levels by inhibiting adenosine transport (e.g., ticagrelor, ethanol, and cannabidiol), affecting intracellular metabolic pathways (e.g., methotrexate, nicotinamide riboside, salicylate, and 5-aminoimidazole-4-carboxamide riboside), or undetermined means (e.g., acupuncture). However, other compounds bind ARs in addition to their canonical 'on-target' activity (e.g., mefloquine). The strength of experimental support for an adenosine-related role in a drug's effects varies widely. AR knockout mice are the 'gold standard' method for investigating an AR role, but few drugs have been tested on these mice. Given the interest in AR modulation for treatment of cancer, CNS, immune, metabolic, cardiovascular, and musculoskeletal conditions, it is informative to consider AR and non-AR adenosinergic effects of approved drugs and conventional treatments.
许多配体直接靶向腺苷受体（ARs）。在这里，我们回顾了非典型 AR 药物对腺苷能信号的影响。非 AR 机制包括通过抑制腺苷转运来提高腺苷水平（例如替格瑞洛、乙醇和大麻二酚）、影响细胞内代谢途径（例如甲氨蝶呤、烟酰胺核苷、水杨酸盐和 5-氨基咪唑-4-羧酰胺核苷）或通过未知手段（例如针灸）。然而，其他化合物除了具有典型的“靶上”活性外，还与 AR 结合（例如甲氟喹）。实验支持药物作用中与腺苷相关的作用的强度差异很大。AR 敲除小鼠是研究 AR 作用的“金标准”方法，但很少有药物在这些小鼠上进行测试。鉴于人们对 AR 调节在癌症、中枢神经系统、免疫、代谢、心血管和肌肉骨骼疾病治疗中的兴趣，考虑已批准药物和常规治疗的 AR 和非 AR 腺苷能作用是有益的。
