Purinergic 2X₁Receptors Mediate Endothelial Dependent Vasodilation to ATP

Abstract

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 2Ј,3Ј-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 Ϫ/Ϫ 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.

Hemoglobin βCys93 is essential for cardiovascular function and integrated response to hypoxia

“…eNOS-coupled endothelial purinergic receptors (37). To eliminate the contribution of this mechanism in assessing SNO-based hypoxic vasodilation, we used aortic ring segments obtained from eNOS-knockout mice (9).…”

Loss of purinergic vascular regulation in the colon during colitis is associated with upregulation of CD39

“…ATP has been shown to be a sympathetic vasoconstrictor in many different vascular beds in a variety of species, including human, rabbit, and mouse mesenteric arteries (2, 28, 32), rabbit ear arteries (17), rat tail (29) and femoral arteries (16), and guinea pig submucosal arterioles (10). ATP released from sympathetic nerve terminals in vascular smooth muscle binds P2X 1 receptors on myocytes and causes vasoconstriction, whereas mechanically induced ATP release from endothelial cells acts on endothelial P2 receptors and leads to vasodilation (3,14,20,32). In the present study, we examined the vasoconstrictor effects of ATP and found that inflammation impedes ATP-induced vasoconstriction.…”

“…The RNA was reprecipitated using LiCl precipitation solution (Ambion). Subsequently, cDNA was reverse transcribed from 1 g of total RNA using SuperScript III (Invitrogen) and oligo(dT) [12][13][14][15][16][17][18] primers (Invitrogen). Real-time PCR was performed using the primers listed in Table 2 with a Roche Lightcycler and the Quantitech SYBR Green PCR kit (Qiagen).…”

Endothelial P2X7 receptors’ expression is reduced by schistosomiasis

“…Although BzATP is a potent agonist of P2X7 receptors, it may also activate other P2X receptors, such as P2X1 and P2X4 receptors [53], and murine mesenteric endothelial cells express the former receptors [32]. Therefore, the residual effect of BzATP observed in the control group in the presence of the P2X7 receptor antagonists, and in endothelial cells from P2X7R −/− mice, might reflect a P2X1 or P2X4 receptor activation and the related NO production.…”

“…Endothelial cells from different vascular beds express both P2Y and P2X receptors, among which P2Y 1 , P2Y 2 , P2Y 11 , [25,26], P2X1, P2X4 and P2X7 [25,[27][28][29] seem to be the main endothelial subtypes. Amongst the welldescribed physiological functions, both P2Y and P2X receptors stimulate endothelial NO production [29][30][31][32][33].…”