Harrington L S, Evans R J, Wray J, Norling L, Swales K E, Vial C, Ali F, Carrier M J, Mitchell J A
Cardiothoracic Pharmacology, UCCM, Cardiac Medicine, the National Heart Lung Institute, Imperial College, London, UK.
Mol Pharmacol. 2007 Nov;72(5):1132-6. doi: 10.1124/mol.107.037325. Epub 2007 Aug 3.
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.
三磷酸腺苷（ATP）是心血管系统中一种重要的内源性介质。它可诱导内皮依赖性血管舒张，但目前对于该反应中激活的确切受体途径仍存在争议。我们使用传统生物测定技术表明，ATP诱导的肠系膜血管舒张是内皮依赖性的。此外，苏拉明和2',3'-O-（2,4,6-三硝基苯基）-ATP（TNP-ATP）均能抑制ATP诱导的血管舒张，这与P2X(1)、P2X(2)或P2X(3)介导的事件一致，并且伊维菌素不会增强该反应，表明这些反应不是由P2X(4)受体介导的。ATP不会诱导P2X(-/-)(1)小鼠的血管舒张，证实了对该受体的绝对需求。最后，在小鼠肠系膜动脉内皮细胞的纯细胞群体中，我们表明P2X(1)信使核糖核酸（mRNA）有特异性表达。然而，与在大脑中的观察结果一致，内皮细胞中存在的P2X(1)似乎不能被传统抗体识别。总之，这些结果表明，ATP诱导的血管舒张是由肠系膜动脉内皮细胞上的P2X(1)受体激活介导的。这些观察结果确立了P2X(1)受体在ATP血管舒张途径中的关键作用。
