Adenosine A3 Receptors in Muscle Protection
Adenosine A3 Receptors in Muscle Protection
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DOI：
10.1007/978-90-481-3144-0_13
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发表时间：
2010-01-01
期刊：
影响因子：
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通讯作者：
Jacobson, Kenneth A.
中科院分区：
文献类型：
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作者：
Liang, Bruce T.;Urso, Maria;Jacobson, Kenneth A.
越来越多的证据表明腺苷a3受体具有重要的细胞保护作用。这种保护功能最初是在改善心脏缺血再灌注损伤中发现的，现在也扩展到骨骼肌。了解各种腺苷受体亚型的药理学，使其选择性激活，并描绘了腺苷a3受体以及其他受体亚型的保护作用。对磷脂酶Cβ2/β3敲除小鼠的研究表明，a3受体诱导的骨骼肌抗缺血保护作用是通过这种磷脂酶同型体介导的。然而，腺苷a1和a2a受体的保护作用不涉及这种磷脂酶c。腺苷a3受体的其他潜在效应物包括katp通道、活性氧、风险-再灌注损伤挽救激酶、mptp -线粒体通透性过渡孔、基质金属蛋白酶和相关金属蛋白酶的组织抑制剂以及金属硫蛋白。腺苷a3受体通过肌细胞表面a3受体介导的直接肌肉保护以及在免疫细胞a3受体水平上发挥的抗炎作用可能有助于腺苷a3受体的有效细胞保护作用。
A growing body of evidence has accumulated to indicate an important cyto-protective role of the adenosine A3receptor. This protective function, originally discovered in ameliorating ischemia–reperfusion injury in the heart, is now also extended to the skeletal muscle. Understanding the pharmacology of various adenosine receptor subtypes allowed their selective activation and delineated the protective role of adenosine A3receptors as well as that of other receptor subtypes. The use of phospholipase Cβ2/β3 knockout mice showed that the A3receptor-induced anti-ischemic protection in the skeletal muscle is mediated via this phospholipase isoform. The protective effect of adenosine A1and A2Areceptors, however, does not involve this phospholipase C. Other potential effectors of the adenosine A3receptor include KATPchannels, reactive oxygen species, RISK-reperfusion injury salvage kinase, mPTP-mitochondrial permeability transition pore, matrix metalloproteinases and associated tissue inhibitor of metallproteinases, and metallothionein. Direct muscle protection mediated via muscle cell-surface A3receptors as well as anti-inflammatory effects exerted at the level of immune cell A3receptors may contribute to the potent cytoprotective effect of the adenosine A3receptor.