Kitazumi K, Mio M, Tasaka K
Department of Pharmacology, Faculty of Pharmaceutical Sciences, Okayama University, Japan.
Biochem Pharmacol. 1991 Aug 8;42(5):1079-85. doi: 10.1016/0006-2952(91)90291-c.
The effects of certain microtubule-disrupting agents on endothelin-1 (ET-1) secretion from porcine aortic endothelial cells were studied. When endothelial cells were treated with thrombin (1 unit/mL), a significant increase in ET-1 secretion was detected in the incubation medium, while ET-1 secretion in the medium was diminished when the cells were treated simultaneously with either colchicine or vinblastine (10(-8)-10(-6) M). In such cases, however, the ET-1 content detected in the cells increased dose-dependently in accordance with the concentrations of the microtubule-disrupting agents. The intracellular accumulation of ET-1 was observed both in mitochondrial and microsomal fractions. On the other hand, thrombin produced a significant increase in polymerized tubulin content without affecting the total tubulin content. A thrombin-induced increase in the intracellular Ca2+ concentration of endothelial cells was inhibited by treatment with either colchicine or vinblastine. These results seem to indicate that the microtubular system may play an important role in ET-1 secretion from endothelial cells.
研究了某些微管破坏剂对猪主动脉内皮细胞内皮素-1(ET-1)分泌的影响。当用凝血酶(1单位/毫升)处理内皮细胞时,在孵育培养基中检测到ET-1分泌显著增加,而当细胞同时用秋水仙碱或长春碱(10⁻⁸ - 10⁻⁶ M)处理时,培养基中的ET-1分泌减少。然而,在这种情况下,细胞中检测到的ET-1含量根据微管破坏剂的浓度呈剂量依赖性增加。在线粒体和微粒体部分均观察到ET-1的细胞内积累。另一方面,凝血酶使聚合微管蛋白含量显著增加,而不影响总微管蛋白含量。用秋水仙碱或长春碱处理可抑制凝血酶诱导的内皮细胞内Ca²⁺浓度升高。这些结果似乎表明微管系统可能在内皮细胞ET-1分泌中起重要作用。