P2Y1 and P2Y2 receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed
P2Y1 and P2Y2 receptors are coupled to the NO/cGMP pathway to vasodilate the rat arterial mesenteric bed
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DOI：
10.1038/sj.bjp.0704789
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发表时间：
2002-07-01
影响因子：
7.3
通讯作者：
Huidobro-Toro, JP
中科院分区：
文献类型：
--
作者：
Buvinic, S;Briones, R;Huidobro-Toro, JP
为了研究核苷酸受体在内皮-平滑肌信号传导中的作用，我们测量了大鼠动脉肠系膜床灌注压的变化、一氧化氮（NO）的腔内输出量和核苷酸灌注后鸟苷3′，5′环单磷酸鸟苷（cGMP）的积累ATP及类似物引起预收缩肠系膜舒张的效价顺序为：2-MeSADP = 2-MeSATP > ADP > ATP = UDP = UTP >腺苷。血管舒张与一氧化氮和cGMP产生的浓度依赖性升高有关。MRS 2179选择性阻断2- mesatp诱导的血管舒张、NO激增和cGMP积累，但对UTP或ATP血管舒张无抑制作用。RT-PCR在完整肠系膜中检测到编码P2Y(1)、P2Y(2)和P2Y(6)受体的mRNA，但未检测到P2Y(4)受体的mRNA。内皮去除后，只发现P2Y(6) mRNA去除内皮或阻断NO合成酶可消除核苷酸引起的扩张、NO升高和cGMP积累。此外，2-MeSATP， ATP， UTP和UDP收缩内皮脱落的肠系膜，显示额外的肌肉P2Y和P2X受体阻断可溶性胍基环化酶可减少2-MeSATP和utp诱导的血管舒张和cGMP的积累，而不干扰NO的产生用IBMX阻断磷酸二酯酶可使2-MeSATP和utp诱导的cGMP升高15-20倍；西地那非仅使cGMP积累增加一倍。NO的升高与cGMP呈线性相关内皮P2Y(1)和P2Y(2)受体偶联到NO/cGMP级联表明细胞外核苷酸参与内皮-平滑肌信号传导。额外的肌肉P2Y和P2X受体强调了核苷酸在血管调节中的生理作用。
1 To assess the role of nucleotide receptors in endothelial-smooth muscle signalling, changes in perfusion pressure of the rat arterial mesenteric bed, the luminal output of nitric oxide (NO) and guanosine 3',5' cyclic monophosphate (cGMP) accumulation were measured after the perfusion of nucleotides.2 The rank order of potency of ATP and analogues in causing relaxation of precontracted mesenteries was: 2-MeSADP = 2-MeSATP > ADP > ATP = UDP = UTP > adenosine. The vasodilatation was coupled to a concentration-dependent rise in NO and cGMP production. MRS 2179 selectively blocked the 2-MeSATP-induced vasodilatation, the NO surge and the cGMP accumulation, but not the UTP or ATP vasorelaxation.3 mRNA encoding for P2Y(1), P2Y(2) and P2Y(6) receptors, but not the P2Y(4) receptor, was detected in intact mesenteries by RT-PCR. After endothelium removal, only P2Y(6) mRNA was found.4 Endothelium removal or blockade of NO synthase obliterated the nucleotides-induced dilatation, the NO rise and cGMP accumulation. Furthermore, 2-MeSATP, ATP, UTP and UDP contracted endothelium-denuded mesenteries, revealing additional muscular P2Y and P2X receptors.5 Blockade of soluble guanylyl cyclase reduced the 2-MeSATP and UTP-induced vasodilatation and the accumulation of cGMP without interfering with NO production.6 Blockade of phosphodiesterases with IBMX increased 15-20 fold the 2-MeSATP and UTP-induced rise in cGMP; sildenafil only doubled the cGMP accumulation. A linear correlation between the rise in NO and cGMP was found.7 Endothelial P2Y(1) and P2Y(2) receptors coupled to the NO/cGMP cascade suggest that extracellular nucleotides are involved in endothelial-smooth muscle signalling. Additional muscular P2Y and P2X receptors highlight the physiology of nucleotides in vascular regulation.