Figure 1.

Schematic diagram illustrating the main receptor subtypes for purines and pyrimidines present in blood vessels involved in control of vascular tone. ATP is released as a cotransmitter with noradrenaline (NA) and neuropeptide Y (NPY) from sympathetic nerves in the adventitia to act at smooth muscle P2X1 receptors and, in some vessels, P2X2, P2X4 and P2Y₁, P2Y₂ and P2Y₆ receptors, resulting in vasoconstriction (and rarely vasodilation); ATP is released with calcitonin gene-related peptide (CGRP) and substance P (SP) from sensory-motor nerves during ‘axon reflex’ activity to act on smooth muscle P2Y receptors, resulting in either vasodilatation or vasoconstriction. P1 (A₁) receptors on nerve terminals of sympathetic and sensory nerves mediate adenosine (arising from ecto-enzymatic breakdown of ATP) modulation of transmitter release. P2X2/3 receptors are present on a subpopulation of sensory nerve terminals. P1 (A₂) receptors on vascular smooth muscle mediate vasodilatation. Endothelial cells release ATP and UTP during shear stress and hypoxia to act on P2Y₁, P2Y₂ and sometimes P2Y₄, P2Y₁₁, P2X1, P2X2, P2X3 and P2X4 receptors, leading to the production of nitric oxide (NO) and subsequent vasodilatation. Adenosine tetraphosphate (AP₄) activates P2X1 receptors to excite smooth muscle. ATP, after its release from aggregating platelets, also acts, together with its breakdown product ADP, on these endothelial receptors. Blood-borne platelets possess P2Y₁ and P2Y₁₂ ADP-selective receptors as well as P2X1 receptors. Immune cells of various kinds possess P2X7 as well as P1, P2X1, P2Y₁ and P2Y₂ receptors. ATP released from red blood cells, which express P2X7 and P2Y₁₃ receptors, is also involved in some circumstances. The additional involvements of uridine adenosine tetraphosphate (Up₄A) described in the paper by Tölle et al. 2010 are indicated in red. (This figure is modified from Burnstock G (1996). J Auton Pharmacol16: 295–302 with permission from Blackwell Science Ltd, UK.)