Figure 1.

Short-term (acute) purinergic signalling controlling vascular tone. Schematic illustrating the main receptor subtypes for purine and pyrimidines present in most blood vessels. Perivascular nerves in the adventitia release ATP as a cotransmitter: ATP is released with noradrenalin (NA) and neuropeptide Y (NPY) from sympathetic nerves to act on smooth muscle P2X₁ and, in some vessels, P2X₂, P2X₄ and P2Y₂ purinoceptors, resulting in vasoconstriction. ATP is also released together with calcitonin gene-related peptide (CGRP) and substance P (SP) from sensory nerves during ‘axon reflex’ activity and broken down to adenosine diphosphate (ADP) to act on smooth muscle P2Y₁ purinoceptors in some regions of some vessels resulting in vasodilatation. P1(A₁) purinoceptors on nerve terminals of sympathetic and sensory nerves mediate adenosine (AD) (arising from enzymatic breakdown of ATP) modulation of transmitter release. P2X_2/3 purinoceptors are present on a subpopulation of sensory nerve terminals. P1(A₂) purinoceptors on vascular smooth muscle mediate vasodilatation. Endothelial cells release ATP and uridine 5′-triphosphate (UTP) during shear stress and hypoxia to act on P2Y₁, P2Y₂ and sometimes P2Y₄ purinoceptors leading to the production of nitric oxide (NO) and subsequent vasodilatation. ATP, following its release from aggregating platelets, also acts on these endothelial receptors. Blood-borne platelets possess P2Y₁ and P2Y₁₂ ADP-selective purinoceptors as well as P2X₁ receptors, while immune cells of various kinds possess P2X₇, as well as P2X₁, P2Y₁ and P2X₂ purinoceptors. P2X₂, P2X₃ and P2X₄ receptors have also been identified on endothelial cell membranes. (Modified from [23], with permission from Lippincott Williams and Wilkins.)