MacCumber M W, Ross C A, Glaser B M, Snyder S H
Department of Neuroscience, Johns Hopkins University School of Medicine, Baltimore, MD 21205.
Proc Natl Acad Sci U S A. 1989 Sep;86(18):7285-9. doi: 10.1073/pnas.86.18.7285.
Endothelin (ET) is a recently identified vasoactive peptide with three isoforms for which three genes have been cloned. The cellular sites of synthesis of this peptide have not yet been identified in vivo. Using Northern blot analysis, we have detected two forms of ET mRNA in rat tissues: a 3.7-kilobase form in the kidney, eye, and brain, a 2.5-kilobase form in the intestine, and both forms in the lung. We have localized these forms of ET mRNA in several rat tissues using in situ hybridization. In the 19-day rat fetus, ET mRNA is highest in the lung, intestine, and meninges. At high resolution, ET mRNA is localized in the lung to respiratory epithelial cells of bronchioles and apparently in blood vessels. In adult tissues, ET mRNA is present throughout the lung, in the renal medulla vasa recta, and in the iris of the eye. ET mRNA is synthesized in close proximity to ET binding sites in many organs (e.g., lung, kidney, intestine, and eye), suggesting a local action of this peptide. However, in other areas (e.g., heart and renal cortex), ET binding sites are present in the absence of ET mRNA, suggesting an action of ET from the bloodstream or from neurons. Northern blot analysis of ET mRNA in microvascular endothelial cells in culture indicates that ET is synthesized in small blood vessels and regulated similarly to its regulation in large vessels. Our results provide evidence that ET, like other regulatory peptides, may serve in several tissues as a neuromodulator or local hormone.
内皮素（ET）是最近发现的一种血管活性肽，有三种异构体，其相应的三个基因已被克隆。该肽在体内的细胞合成位点尚未确定。我们通过Northern印迹分析，在大鼠组织中检测到两种形式的ET mRNA：一种3.7千碱基的形式存在于肾脏、眼睛和大脑中，一种2.5千碱基的形式存在于肠道中，两种形式在肺中均有。我们利用原位杂交技术将这些形式的ET mRNA定位在几种大鼠组织中。在19天龄的大鼠胎儿中，ET mRNA在肺、肠道和脑膜中含量最高。高分辨率观察时，ET mRNA在肺中定位于细支气管的呼吸上皮细胞，明显也存在于血管中。在成体组织中，ET mRNA存在于整个肺、肾髓质直小血管和眼睛的虹膜中。ET mRNA在许多器官（如肺、肾、肠道和眼睛）中与其结合位点紧密合成，提示该肽具有局部作用。然而，在其他区域（如心脏和肾皮质），ET结合位点存在但无ET mRNA，提示ET可能来自血流或神经元。对培养的微血管内皮细胞中ET mRNA的Northern印迹分析表明，ET在小血管中合成，其调控方式与大血管相似。我们的结果提供了证据，表明ET与其他调节肽一样，在几种组织中可能作为神经调节剂或局部激素发挥作用。
