Hartley S A, Kato K, Salter K J, Kozlowski R Z
University of Oxford, Department of Pharmacology, Oxford, UK.
Circ Res. 1998 Nov 2;83(9):940-6. doi: 10.1161/01.res.83.9.940.
Uridine nucleotides are known to cause constriction of pulmonary arterial smooth muscle. However, the P2 receptor subtypes underlying the contractile effects of these nucleotides in the pulmonary circulation have not been determined. We have used myography and the patch-clamp recording technique to compare the effects of UTP and UDP in isolated small pulmonary arteries (diameter 100 to 400 microm) and their constituent smooth muscle cells. In endothelium-denuded arteries, both UTP and UDP (0.01 to 3 mmol/L) induced concentration-dependent increases in tension that were independent of P2X receptor stimulation. The UDP-mediated increase in tension was significantly less sensitive to the nonselective P2 receptor blocker suramin than the UTP-mediated increase in tension. In single isolated arterial myocytes, voltage-clamped at -50 mV (close to the resting membrane potential of these cells), application of both UTP and UDP evoked periodic oscillations of inward current primarily because of a Ca2+-activated Cl- current (ICl,Ca). Oscillations of ICl,Ca evoked by UTP were reversibly inhibited by suramin, although those evoked by UDP were insensitive to the antagonist. In addition to confirming the presence of classical P2Y2 receptors, these results also provide functional evidence for the existence of a novel UDP receptor in pulmonary arterial myocytes, which may contribute to pyrimidine-evoked vasoconstriction. This notion is supported by molecular evidence that demonstrates the presence of P2Y6 receptor transcripts in rat pulmonary arterial smooth muscle.
已知尿苷核苷酸可引起肺动脉平滑肌收缩。然而，这些核苷酸在肺循环中的收缩作用所涉及的P2受体亚型尚未确定。我们使用肌动描记法和膜片钳记录技术，比较了UTP和UDP对分离的小肺动脉（直径100至400微米）及其组成的平滑肌细胞的影响。在内皮剥脱的动脉中，UTP和UDP（0.01至3 mmol/L）均引起张力的浓度依赖性增加，且这种增加与P2X受体刺激无关。UDP介导的张力增加对非选择性P2受体阻滞剂苏拉明的敏感性明显低于UTP介导的张力增加。在单个分离的动脉肌细胞中，电压钳制在-50 mV（接近这些细胞的静息膜电位），施加UTP和UDP均引发内向电流的周期性振荡，主要是由于Ca2+激活的Cl-电流（ICl,Ca）。UTP诱发的ICl,Ca振荡可被苏拉明可逆性抑制，而UDP诱发的振荡对该拮抗剂不敏感。除了证实经典P2Y2受体的存在外，这些结果还为肺动脉肌细胞中存在一种新型UDP受体提供了功能证据，该受体可能参与嘧啶诱发的血管收缩。这一观点得到了分子证据的支持，该证据表明大鼠肺动脉平滑肌中存在P2Y6受体转录本。
