Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Southport, QLD, Australia.
Pharmacol Ther. 2013 Oct;140(1):92-111. doi: 10.1016/j.pharmthera.2013.06.002. Epub 2013 Jun 10.
Intra- and extracellular adenosine levels rise in response to physiological stimuli and with metabolic/energetic perturbations, inflammatory challenge and tissue injury. Extracellular adenosine engages members of the G-protein coupled adenosine receptor (AR) family to mediate generally beneficial acute and adaptive responses within all constituent cells of the heart. In this way the four AR sub-types-A1, A2A, A2B, and A3Rs-regulate myocardial contraction, heart rate and conduction, adrenergic control, coronary vascular tone, cardiac and vascular growth, inflammatory-vascular cell interactions, and cellular stress-resistance, injury and death. The AR sub-types exert both distinct and overlapping effects, and may interact in mediating these cardiovascular responses. The roles of the ARs in beneficial modulation of cardiac and vascular function, growth and stress-resistance render them attractive therapeutic targets. However, interactions between ARs and with other receptors, and their ubiquitous distribution throughout the body, can pose a challenge to the implementation of site- and target-specific AR based pharmacotherapy. This review outlines cardiovascular control by adenosine and the AR family in health and disease, including interactions between AR sub-types within the heart and vessels.
细胞内外的腺苷水平会响应生理刺激和代谢/能量紊乱、炎症挑战和组织损伤而升高。细胞外腺苷与 G 蛋白偶联腺苷受体 (AR) 家族的成员结合，在心脏的所有组成细胞中介导通常有益的急性和适应性反应。通过这种方式，四种 AR 亚型-A1、A2A、A2B 和 A3R-调节心肌收缩、心率和传导、肾上腺素能控制、冠状血管张力、心脏和血管生长、炎症-血管细胞相互作用以及细胞应激抗性、损伤和死亡。AR 亚型发挥着独特和重叠的作用，并可能在介导这些心血管反应中相互作用。AR 在有益调节心脏和血管功能、生长和应激抗性方面的作用使它们成为有吸引力的治疗靶点。然而，AR 之间以及与其他受体之间的相互作用，以及它们在全身的广泛分布，可能会对基于 AR 的靶向和特定部位药理学治疗的实施构成挑战。这篇综述概述了腺苷和 AR 家族在健康和疾病中的心血管控制作用，包括心脏和血管内 AR 亚型之间的相互作用。
