Up4A stimulates endothelium-independent contraction of isolated rat pulmonary artery
Up4A stimulates endothelium-independent contraction of isolated rat pulmonary artery
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DOI：
10.1152/ajplung.00403.2007
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发表时间：
2008-04-01
影响因子：
4.9
通讯作者：
Zheng, Xi-Long
中科院分区：
文献类型：
--
作者：
Gui, Yu;Walsh, Michael P.;Zheng, Xi-Long
细胞外核苷酸如ATP、UDP和UTP通过P2 X和P2 Y受体调节肺血管张力。尿苷腺苷四磷酸（Up（4）A）是近年来发现的一种新的内皮源性缩血管因子。Up（4）A含有嘌呤和嘧啶部分，其潜在地激活P2 X和P2 Y受体。本文观察了Up（4）A对离体大鼠肺动脉收缩力的影响。1-100 μ M的Up（4）A以浓度依赖性方式刺激收缩。Up 4A在内皮剥脱的动脉中与UTP和UDP等效，而在内皮完整的制备物中比UTP和UDP有效得多。Up（4）A的血管收缩作用可被苏拉明抑制，但不被IP 5I或α，β-亚甲基-ATP（α，β-Me-ATP）对P2 X受体的脱敏所抑制。用毒胡萝卜素、尼群地平或EGTA预处理也能抑制UP（4）A诱导的收缩，但不受H1152的影响。此外，与ATP和UTP不同，Up（4）A不诱导苯肾上腺素预收缩的内皮完整制剂的舒张。提示Up（4）A对大鼠肺动脉有强的缩血管作用，但不是扩血管作用。Up（4）A可能通过对苏拉明敏感的P2 Y受体起作用。Up（4）A的收缩作用涉及细胞外Ca 2（+）的进入和细胞内Ca 2（+）的释放，但不涉及通过RhoA/Rho激酶途径的Ca 2（+）敏化。因此，UP（4）A在肺血管张力的调节中可能起重要作用。
Extracellular nucleotides, such as ATP, UDP, and UTP, regulate pulmonary vascular tone through P2X and P2Y receptors. Recently, uridine adenosine tetraphosphate (Up(4)A) was reported as a novel endothelium-derived vasoconstrictive factor. Up(4)A contains both purine and pyrimidine moieties, which potentially activate P2X and P2Y receptors. The present study examined the effect of Up(4)A on contractility of isolated rat pulmonary artery. Up(4)A at 1-100 mu M stimulated contraction in a concentration-dependent manner. Up4A was equipotent as UTP and UDP in the endothelium-denuded artery while much more effective than UTP and UDP in endothelium-intact preparations. The vasoconstrictor effect of Up(4)A was inhibited by suramin but not IP5I or desensitization of P2X receptors with alpha,beta-methylene-ATP (alpha,beta-Me-ATP). Up(4)A-induced contraction was also inhibited by pretreatment with thapsigargin, nitrendipine, or EGTA but unaffected by H1152. Furthermore, unlike ATP and UTP, Up(4)A did not induce relaxation of endothelium-intact preparations precontracted with phenylephrine. These results suggest that Up(4)A is a potent vasoconstrictor, but not a vasodilator, of the rat pulmonary artery. Up(4)A likely acts through a suramin-sensitive P2Y receptor. The contractile effect of Up(4)A involves the entry of extracellular Ca2(+) and release of Ca2(+) from intracellular stores but not Ca2(+) sensitization via the RhoA/Rho kinase pathway. Up(4)A, therefore, potentially plays an important role in the regulation of pulmonary vascular tone.