Yokokawa K, Kohno M, Johchi M, Horio T, Murakawa K, Yasunari K, Yanagisawa M, Takeda T
First Department of Internal Medicine, Osaka City University Medical School, Japan.
Life Sci. 1993;53(21):1631-41. doi: 10.1016/0024-3205(93)90187-8.
Endothelin (ET)-1 causes mesangial cell contraction and proliferation. The present study was designed to evaluate the functional ET receptor subtype in cultured rat mesangial cells by measuring intracellular Ca2+ signaling with the use of a newly synthesized ET receptor type A selective antagonist-BQ123. The ET-1, ET-2 and ET-3 increased intracellular Ca2+ level in a dose-dependent manner. BQ-123 suppressed intracellular Ca2+ elevation in response to ET-1 in a dose-dependent manner with its half maximal inhibition value of 28 nM. BQ-123 (10(-6) M) did not affect ET-3 (10(-7) M)-induced Ca2+ response. The peak Ca2+ levels after addition of ET-3 without BQ-123 were similar to those in response to ET-1, ET-2 and ET-3 in the presence of BQ-123. Northern blot analysis showed that cultured mesangial cells expressed both ETA and ETB receptor mRNA. These results suggest that cultured mesangial cells have, at least, two types of functional receptors, one of which is an ETA receptor.
内皮素（ET）-1可引起系膜细胞收缩和增殖。本研究旨在通过使用新合成的A型内皮素受体选择性拮抗剂——BQ123测量细胞内Ca2+信号，评估培养的大鼠系膜细胞中的功能性内皮素受体亚型。ET-1、ET-2和ET-3以剂量依赖性方式增加细胞内Ca2+水平。BQ-123以剂量依赖性方式抑制ET-1诱导的细胞内Ca2+升高，其半数最大抑制值为28 nM。BQ-123（10^(-6) M）不影响ET-3（10^(-7) M）诱导的Ca2+反应。在不添加BQ-123的情况下添加ET-3后的Ca2+峰值水平，与在存在BQ-123的情况下对ET-1、ET-2和ET-3反应时的峰值水平相似。Northern印迹分析表明，培养的系膜细胞表达ETA和ETB受体mRNA。这些结果表明，培养的系膜细胞至少有两种功能性受体，其中一种是ETA受体。
