Murphy H S, Maroughi M, Till G O, Ward P A
Department of Pathology, University of Michigan Medical School, Ann Arbor 48109.
Am J Physiol. 1994 Aug;267(2 Pt 1):L145-51. doi: 10.1152/ajplung.1994.267.2.L145.
Stimulation of rat pulmonary artery endothelial cells (RPAEC) with phorbol 12-myristate 13-acetate (PMA) resulted in an increase in intracellular calcium ([Ca2+]i). Unlike the response to bradykinin, C5a and tumor necrosis factor-alpha (TNF-alpha) previously reported (15), the PMA-induced increase in [Ca2+]i was predominantly dependent on extracellular calcium. The PMA response paralleled the BAY K 8644-induced, extracellular calcium-dependent increase in [Ca2+]i. Pretreatment of endothelial cells with the protein kinase C inhibitor staurosporine resulted in a concentration-dependent inhibition of the increase in [Ca2+]i in response to PMA. The ability of PMA analogues to induce significant increase in [Ca2+]i paralleled their ability to induce O2- generation in neutrophils. The PMA-induced influx of extracellular Ca2+ was inhibited by the L-channel selective antagonists diltiazem, nifedipine, nicardipine, and verapamil in a dose-dependent manner. Depolarizing conditions induced by high [K+]o enhanced the calcium response to PMA. The data presented are consistent with the hypothesis that PMA-induced increases in [Ca2+]i in endothelial cells are the result of Ca2+ influx through voltage-dependent L-type Ca2+ channels.
用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）刺激大鼠肺动脉内皮细胞（RPAEC）会导致细胞内钙浓度（[Ca2+]i）升高。与先前报道的对缓激肽、C5a和肿瘤坏死因子-α（TNF-α）的反应不同（15），PMA诱导的[Ca2+]i升高主要依赖于细胞外钙。PMA反应与BAY K 8644诱导的、依赖细胞外钙的[Ca2+]i升高相似。用蛋白激酶C抑制剂星形孢菌素预处理内皮细胞会导致对PMA反应的[Ca2+]i升高受到浓度依赖性抑制。PMA类似物诱导[Ca2+]i显著升高的能力与其诱导中性粒细胞产生O2-的能力相似。L通道选择性拮抗剂地尔硫卓、硝苯地平、尼卡地平和维拉帕米以剂量依赖性方式抑制PMA诱导的细胞外Ca2+内流。高[K+]o诱导的去极化条件增强了对PMA的钙反应。所呈现的数据与以下假设一致，即PMA诱导内皮细胞[Ca2+]i升高是Ca2+通过电压依赖性L型Ca2+通道内流的结果。
