Adenosine Receptor Profiling Reveals an Association between the Presence of Spare Receptors and Cardiovascular Disorders

Figures

• 

  Figure 1. Adenosine metabolism and mechanisms. ADA: adenosine deaminase; AMP: adenosine monophosphate; ATP: adenosine triphosphate; AVB: atrioventricular block; ENT: equilibrative nucleoside transporter; SAH: S adenosyl-homocysteine; XO: xanthine oxidase; RBC: red blood cell.

• 

  Figure 2. Adenosine receptor activation and cAMP production. The activation of effector cells by adenosine either increases (via A2 receptor) or decreases (via A1 receptor) cAMP production according to the cell type. Effects are indicated for illustration purposes (e.g., chronotropy, vasodilation). Ado: adenosine; A1R: A1 receptor; A2R: A2 receptor; AC: adenylylcyclase; Gs: G stimulating; Gi: G inhibiting; AVB: atrioventricular block. There is a direct relationship between cAMP production and biological effects.

• 

  Figure 3. Relationship between EC50 and KD regarding A2AR expressed in the lymphocytes of a coronary artery disease patient. Dose–response curves resulting from binding of an agonist to A2AR expressed on the surface of lymphocytes isolated from a patient with ischemia induced by the exercise stress test (EST). White circles: cAMP production. Black circles: agonist binding. The fact that EC50 < < KD indicates the presence of a receptor reserve (after ref. [35], with modifications).

• 

  Figure 4. Spare A2A receptors and coronary artery disease. During the EST, the adenosine plasma level (APL) increases to improve di-oxygen supply to the myocardium by increasing coronary artery diameter, and hence blood flow. In the absence of spare A2A receptors, increase in APL leads to coronary vasodilation via A2A receptor activation and cAMP production, cAMP production and vasodilation being correlated. In the presence of spare A2A receptors, the production of cAMP in basal conditions is already maximal and cannot be further increased when di-oxygen supply needs to be increased during EST, because APL level is much above the EC50 value: no significant coronary vasodilation occurs.

• 

  Figure 5. Spare A2A receptors and neurocardiogenic syncopes. In the absence of spare A2A receptors, the activation of target cells by adenosine leads to cAMP production and biological effects that are proportional to adenosine plasma levels (APL; left panel). In the presence of spare A2A receptors, a weak increase in APL leads to a dramatic drop in blood pressure due to strong and rapid vasodilation, auriculo–ventricular block, or both (right panel).