Tosun M, Paul R J, Rapoport R M
Department of Pharmacology and Cell Biophysics, University of Cincinnati, Ohio, USA.
J Pharmacol Exp Ther. 1998 Mar;284(3):921-8.
The purpose of this study was to investigate the role of extracellular Ca++ influx via L-type and non-L-type Ca++ channels in thromboxane A2 receptor-mediated contraction. In intact rat aorta, U46619, a selective thromboxane A2 receptor agonist, induced concentration-dependent increases in intracellular Ca++ ([Ca++]i) and contraction (EC50 values of 5.5 and 6.1 nM, respectively). U46619 (10 nM) induced approximately 60 to 70% of maximal [Ca++]i elevation and contraction. Treatment with verapamil, an L-type Ca++ channel blocker, before 10 nM U46619 challenge, or during the plateau [Ca++]i elevation and contraction, decreased these parameters by approximately 50%. Ni++, a nonselective blocker of cation channels, or SKF96365, a purported blocker of receptor-operated Ca++ channels, further decreased the contraction and abolished the [Ca++]i elevation that remained after verapamil treatment of 10 nM U46619-challenged vessels. Pretreatment with verapamil and Ni++ to prevent Ca++ influx and with cyclopiazonic acid to deplete [Ca++]i stores also partially prevented U46619-induced contraction, whereas [Ca++]i elevation was abolished. These results suggest that thromboxane A2 receptor-mediated contraction of vascular smooth muscle partly depends on the influx of extracellular Ca++ via both L-type and non-L-type Ca++ channels, as well as a mechanism independent of [Ca++]i elevation.
本研究的目的是探讨细胞外Ca++通过L型和非L型Ca++通道内流在血栓素A2受体介导的收缩中的作用。在完整的大鼠主动脉中，选择性血栓素A2受体激动剂U46619引起细胞内Ca++（[Ca++]i）浓度依赖性增加和收缩（EC50值分别为5.5和6.1 nM）。U46619（10 nM）引起最大[Ca++]i升高和收缩的约60%至70%。在10 nM U46619刺激前或在[Ca++]i升高和收缩的平台期用L型Ca++通道阻滞剂维拉帕米治疗，可使这些参数降低约50%。阳离子通道的非选择性阻滞剂Ni++或据称的受体操纵性Ca++通道阻滞剂SKF96365进一步降低了收缩，并消除了维拉帕米处理10 nM U46619刺激的血管后剩余的[Ca++]i升高。用维拉帕米和Ni++预处理以防止Ca++内流，并用环匹阿尼酸耗尽[Ca++]i储存，也部分阻止了U46619诱导的收缩，而[Ca++]i升高被消除。这些结果表明，血栓素A2受体介导的血管平滑肌收缩部分取决于细胞外Ca++通过L型和非L型Ca++通道的内流，以及一种独立于[Ca++]i升高的机制。
