Purinergic 2X1 receptors mediate endothelial dependent vasodilation to ATP.
ATP is an important endogenous mediator in the cardiovascular system. It induces endothelium dependent vasodilation, but the precise receptor pathway activated in this response is currently under debate. We have used traditional bioassay techniques to show that ATP-induced vasodilation in mesenteric vessels is endothelium-dependent. Furthermore, ATP-induced vasodilation was inhibited by both suramin and 2',3'-O-(2,4,6-trinitrophenyl)-ATP (TNP-ATP), consistent with a P2X(1)-, P2X(2)-, or P2X(3)-mediated event and was not potentiated by ivermectin, indicating that these responses were not P2X(4) receptor-mediated. ATP did not induce vasodilation in vessels from P2X (-/-)(1) mice, confirming an absolute requirement for this receptor. Finally, in pure cell populations of mouse mesenteric artery endothelial cells, we show that P2X(1) mRNA is specifically expressed. However, in line with observations in the brain, the P2X(1) present in endothelial cells does not seem to be recognized by conventional antibodies. Together, these results show that ATP-induced vasodilation is mediated by P2X(1) receptor activation on mesenteric arterial endothelial cells. These observations establish a critical role for P2X(1) receptors in the ATP vasodilator pathway.
Cardiothoracic Pharmacology, UCCM, Cardiac Medicine, the National Heart Lung Institute, Imperial College, London, UK. l.harrington@imperial.ac.uk
L S
LS
Harrington
R J
RJ
Evans
J
J
Wray
L
L
Norling
K E
KE
Swales
C
C
Vial
F
F
Ali
M J
MJ
Carrier
J A
JA
Mitchell
D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid / Q000494:pharmacology; D000109:Acetylcholine / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000818:Animals; D001681:Biological Assay; D004730:Endothelium, Vascular / Q000187:drug effects* / Q000502:physiology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008817:Mice, Mutant Strains; D009599:Nitroprusside / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2 / Q000235:genetics / Q000502:physiology; D058469:Receptors, Purinergic P2X; D058848:Receptors, Purinergic P2X4; D014662:Vasoconstrictor Agents / Q000494:pharmacology; D014664:Vasodilation / Q000187:drug effects / Q000235:genetics; D014665:Vasodilator Agents / Q000494:pharmacology*
C548227:P2rx4 protein, mouse; D058910:Purinergic P2 Receptor Agonists; D018048:Receptors, Purinergic P2; D058469:Receptors, Purinergic P2X; D058848:Receptors, Purinergic P2X4; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D009599:Nitroprusside; C045674:2',3'-O-(2,4,6-trinitro-cyclohexadienylidine)adenosine 5'-triphosphate; D011189:Potassium Chloride; D019796:15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid; D000255:Adenosine Triphosphate; D000109:Acetylcholine