Fig. 1.

P2 receptor-mediated regulation of the circulation. See text for details. Purines and pyrimidines are released on the luminal side from endothelial cells, platelets and red blood cells (RBC) in response to hypoxia, acidosis, adrenaline, shear stress and other stimuli. When the endothelial cell layer is intact, the response is vasodilatation by the endothelial release of nitric oxide (NO), endothelium-derived hyperpolarising factor (EDHF) and prostaglandins (Pgl). When the endothelium is damaged, platelets accumulate, release ATP and ADP and mediate vasoconstriction via P2 receptors on the vascular smooth muscle cell (VSMC). On the adventitial side sympathetic and sensory nerves mediate vasoconstriction. Extracellular nucleotides are rapidly degraded by NTPDase1 on endothelium reducing ATP to AMP, followed by conversion to adenosine by CD73 (not shown). In the subendothelium NTPDase2 is present, degrading ATP to ADP, maintaining the platelet activating and contractile effects. Ado adenosine, CGRP calcitonin gene-related peptide, SP substance P