title: Cardiovascular adenosine receptors: expression, actions and interactions.
abstract: 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.
authors.affiliation: Heart Foundation Research Centre, Griffith Health Institute, Griffith University, Southport, QLD, Australia. Electronic address: j.headrick@griffith.edu.au.
authors.forename: John P
authors.initials: JP
authors.lastname: Headrick
authors.forename: Kevin J
authors.initials: KJ
authors.lastname: Ashton
authors.forename: Roselyn B
authors.initials: RB
authors.lastname: Rose'meyer
authors.forename: Jason N
authors.initials: JN
authors.lastname: Peart
mesh_terms: D000241:Adenosine / Q000502:physiology; D000818:Animals; D002318:Cardiovascular Diseases / Q000378:metabolism / Q000503:physiopathology; D006321:Heart / Q000502:physiology*; D006801:Humans; D018047:Receptors, Purinergic P1 / Q000502:physiology*
chemical_list: D018047:Receptors, Purinergic P1; D000241:Adenosine
keywords: ADP; AMP; ANP; AR; ATP; ATP-gated K(+) channel; AV; Adenosine receptors; Angiogenesis; CRE; Cardioprotection; Contractility; ECM; G-protein coupled receptor; GPCR; HIF; Heart rate; IFN; IL-; IMP; K(ATP); MMP; NO; P(i); PI3K; PKC; PostCon; PreCon; Remodeling; SA; TNFα; UTR; VEGF; adenosine diphosphate; adenosine monophosphate; adenosine receptor; adenosine triphosphate; atrial natriuretic peptide; atrioventricular; cAMP response element; extracellular matrix; hypoxia inducible factor; inorganic phosphate; inosine monophosphate; interferon; interleukin; matrix metalloproteinase; nitric oxide; phosphoinositide 3-kinase; postconditioning; preconditioning; protein kinase C; sinoatrial; tumor necrosis factor α; untranslated region; vascular endothelial growth factor