International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors.
International Union of Pharmacology. XXV. Nomenclature and classification of adenosine receptors.
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DOI：
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发表时间：
2001-12
影响因子：
21.1
通讯作者：
B. Fredholm;A. IJzerman;K. Jacobson;K. Klotz;J. Linden
中科院分区：
文献类型：
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作者：
B. Fredholm;A. IJzerman;K. Jacobson;K. Klotz;J. Linden
四腺苷受体已被克隆和表征从几个哺乳动物物种。这些受体被命名为腺苷A（1）、A（2A）、A（2B）和A（3）。A（2A）和A（2B）受体优选与G蛋白的G（s）家族的成员相互作用，而A（1）和A（3）受体与G（i/o）蛋白相互作用。然而，其他G蛋白相互作用也被描述。腺苷是所有这些受体的优选内源性激动剂，但肌苷也可以激活A（3）受体。在基础条件下观察到的腺苷水平足以引起所有受体的某种激活，至少在它们大量表达的地方。例如，局部缺血可激活所有受体，即使在低丰度表达时。因此，用受体拮抗剂和靶向破坏腺苷A（1）、A（2A）和A（3）表达的小鼠进行的实验揭示了这些受体在生理和特别是病理生理条件下的作用。有药理学工具可用于分类A（1），A（2A）和A（3）受体，但很少有药物选择性地与A（2B）受体相互作用。这些药物与其受体相互作用的可测试模型已通过定点诱变和基于同源性的建模产生。激动剂和拮抗剂都被开发为潜在的药物。
Four adenosine receptors have been cloned and characterized from several mammalian species. The receptors are named adenosine A(1), A(2A), A(2B), and A(3). The A(2A) and A(2B) receptors preferably interact with members of the G(s) family of G proteins and the A(1) and A(3) receptors with G(i/o) proteins. However, other G protein interactions have also been described. Adenosine is the preferred endogenous agonist at all these receptors, but inosine can also activate the A(3) receptor. The levels of adenosine seen under basal conditions are sufficient to cause some activation of all the receptors, at least where they are abundantly expressed. Adenosine levels during, e.g., ischemia can activate all receptors even when expressed in low abundance. Accordingly, experiments with receptor antagonists and mice with targeted disruption of adenosine A(1), A(2A), and A(3) expression reveal roles for these receptors under physiological and particularly pathophysiological conditions. There are pharmacological tools that can be used to classify A(1), A(2A), and A(3) receptors but few drugs that interact selectively with A(2B) receptors. Testable models of the interaction of these drugs with their receptors have been generated by site-directed mutagenesis and homology-based modelling. Both agonists and antagonists are being developed as potential drugs.