Muller C E
Pharmaceutical Institute, University of Bonn, Bonn, Germany.
Curr Med Chem. 2000 Dec;7(12):1269-88. doi: 10.2174/0929867003374101.
Developments in the field of adenosine receptor (AR) agonists of the past years are presented and discussed. Four different AR subtypes, A(1), A(2A), A(2B), and A(3), have been cloned from different species including the human receptors. Recombinant ARs expressed in permanent mammalian cell lines have found wide application in the screening of new ligands. Considerable differences are observed among data from different laboratories, using recombinant receptors for the assays. Reevaluation of compounds at all four receptor subtypes has shown that agonists that were believed to be selective for either A(1) or A(2A) ARs may be potent A(3) agonists and thus, non-selective. Potent and selective agonists for two of the AR subtypes, A(1) and A(3), have been developed. Truly selective A(2A) AR agonists, however, are presently not available. Potent or selective A(2B) agonists are still lacking. Since the treatment with AR agonists may lead to fast desensitization of the receptors, partial agonists, and indirect AR agonists, such as adenosine kinase inhibitors, or allosteric enhancers of adenosine binding, are being developed as site- and event-specific agents.
本文介绍并讨论了过去几年腺苷受体（AR）激动剂领域的发展情况。已从包括人类受体在内的不同物种中克隆出四种不同的AR亚型，即A(1)、A(2A)、A(2B)和A(3)。在永久性哺乳动物细胞系中表达的重组AR在新配体筛选中得到了广泛应用。使用重组受体进行检测时，不同实验室的数据存在显著差异。对所有四种受体亚型的化合物重新评估表明，那些被认为对A(1)或A(2A) AR具有选择性的激动剂可能是强效的A(3)激动剂，因此是非选择性的。已开发出针对AR亚型中的两种，即A(1)和A(3)的强效且选择性激动剂。然而，目前尚无真正选择性的A(2A) AR激动剂。强效或选择性的A(2B)激动剂仍然缺乏。由于用AR激动剂治疗可能导致受体快速脱敏，因此正在开发部分激动剂、间接AR激动剂，如腺苷激酶抑制剂或腺苷结合的变构增强剂，作为位点特异性和事件特异性药物。
