Headrick John P, Peart Jason
Heart Foundation Research Centre, Griffith University Gold Coast Campus, Southport, QLD 4217, Australia.
Vascul Pharmacol. 2005 Apr-May;42(5-6):271-9. doi: 10.1016/j.vph.2005.02.009. Epub 2005 Apr 19.
The A3 adenosine receptor (A3AR) is attributed with multiple beneficial actions in ischemic-reperfused myocardium, including modulation of oncotic and apoptotic cell death and enhancement of contractile function. Additionally, the A3AR may attenuate vascular dysfunction and improve long-term outcome from myocardial insult (modulating hypertrophy and angiogenesis). Available evidence indicates that this receptor sub-type is minimally activated by endogenous adenosine during ischemia (A3AR antagonists exerting no effects on ischemic outcome), and is thus amenable to activation with exogenous agonists. Protected phenotypes arise with both pre- and post-ischemic treatment with A3AR agonists, and transient A3AR agonism also triggers early and delayed preconditioned states. The molecular basis for the varied protective actions of the A3AR remains poorly defined, and may well vary between species (e.g. rodent vs. human) and protective responses (e.g. acute vs. delayed protection). Nonetheless, A3ARs may be more promising as therapeutic "anti-ischemic" targets compared with other adenosine receptor subtypes, since A3AR agonists elicit fewer and less significant side-effects. This review addresses current knowledge and controversy regarding the protective actions (and associated signaling) of A3ARs in ischemic-reperfused heart.
A3腺苷受体（A3AR）在缺血再灌注心肌中具有多种有益作用，包括调节渗透性和凋亡性细胞死亡以及增强收缩功能。此外，A3AR可能减轻血管功能障碍并改善心肌损伤后的长期预后（调节肥大和血管生成）。现有证据表明，该受体亚型在缺血期间被内源性腺苷激活的程度极低（A3AR拮抗剂对缺血结局无影响），因此适合用外源性激动剂激活。缺血前和缺血后用A3AR激动剂治疗均可产生保护表型，短暂的A3AR激动也会触发早期和延迟的预处理状态。A3AR各种保护作用的分子基础仍不清楚，并且很可能因物种（例如啮齿动物与人类）和保护反应（例如急性与延迟保护）而异。尽管如此，与其他腺苷受体亚型相比，A3AR作为治疗性“抗缺血”靶点可能更有前景，因为A3AR激动剂引起的副作用更少且不那么明显。本综述阐述了关于A3AR在缺血再灌注心脏中的保护作用（及相关信号传导）的现有知识和争议。
