Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Melbourne, VIC, Australia.
Department of Pharmacology, Monash University, Melbourne, VIC, Australia.
Br J Pharmacol. 2018 Nov;175(21):4036-4046. doi: 10.1111/bph.14337. Epub 2018 Jun 21.
Adenosine receptors are a family of GPCRs containing four subtypes (A , A , A and A receptors), all of which bind the ubiquitous nucleoside adenosine. These receptors play an important role in physiology and pathophysiology and therefore represent attractive drug targets for a range of conditions. The theoretical framework surrounding drug action at adenosine receptors now extends beyond the notion of prototypical agonism and antagonism to encompass more complex pharmacological concepts. New paradigms include allostery, in which ligands bind a topographically distinct receptor site from that of the endogenous agonist, homomeric or heteromeric interactions across receptor oligomers and biased agonism, that is, ligand-dependent differential intracellular signalling. This review provides a concise overview of allostery, oligomerization and biased agonism at adenosine receptors and outlines how these paradigms may enhance future drug discovery endeavours focussed on the development of novel therapeutic agents acting at adenosine receptors.
This article is part of a themed section on Molecular Pharmacology of GPCRs. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
腺苷受体是 GPCR 家族的一个成员，包含四个亚型（A 、A 、A 和 A 受体），它们都与普遍存在的核苷腺苷结合。这些受体在生理和病理生理学中起着重要作用，因此代表了一系列疾病的有吸引力的药物靶点。围绕腺苷受体药物作用的理论框架现在已经超越了典型激动剂和拮抗剂的概念，包含了更复杂的药理学概念。新的范例包括变构作用，其中配体与内源性激动剂的拓扑上不同的受体结合位点结合，受体寡聚体之间的同型或异型相互作用以及偏向激动作用，即配体依赖性的差异细胞内信号转导。本文简要概述了腺苷受体的变构作用、寡聚作用和偏向激动作用，并概述了这些范例如何增强未来专注于开发新型治疗剂以作用于腺苷受体的药物发现努力。
本文是 GPCR 分子药理学专题的一部分。要查看本部分中的其他文章，请访问 http://onlinelibrary.wiley.com/doi/10.1111/bph.v175.21/issuetoc.
