Fig. 4.

Schematic diagram of the adenine nucleotide hypothesis of negative feedback coronary control. Oxygen (O₂) is released from hemoglobin (Hb) in coronary capillaries in response to myocardial oxygen consumption. Deoxyhemoglobin facilitates the release of ATP from red blood cells (RBC) that acts on endothelial purinergc P2Y₁ receptors to initiate a retrograde conducted response via gap junctions connecting endothelial cells. The conducted signals dilate the upstream arteriole smooth muscle cells via gap junctions and the release of nitric oxide (NO). Nucleotidases (NTase) in the plasma and on the surface of endothelial cells break ATP down to ADP, which activates P2Y₁ receptors. ADP also activates P2Y₁₃ receptors on the surface of RBC to inhibit the further release of ATP from RBC. ADP is broken down to AMP, which activates P1 receptors to generate a retrograde conducted vasodilator response. AMP is degraded to adenosine (ADO) that is rapidly taken up by RBC and endothelial cells.