Anggård E, Galton S, Rae G, Thomas R, McLoughlin L, de Nucci G, Vane J R
William Harvey Research Institute, St. Bartholomew's Hospital Medical College, London, England.
J Cardiovasc Pharmacol. 1989;13 Suppl 5:S46-9; discussion S74. doi: 10.1097/00005344-198900135-00012.
Endothelin-1 (ET-1) has been isolated from cultured endothelial cells and might have a role in cardiovascular regulation. To study the fate of labeled ET-1, we prepared [125I]-labeled ET-1 (formerly porcine and human ET) and ET-3 (formerly rat ET). Approximately 0.2 microCi (0.2 pmol) was injected into the left ventricle of anesthetized rats and blood samples analyzed for radioactivity for up to 40 min. The animals were then killed and the distribution of radioactivity determined in various organs. Both ET-1 and ET-3 were rapidly removed from the circulation, with more than 60% of the removal occurring in the first minute. Removal of ET-1 was somewhat faster than that of ET-3. The highest uptake of radioactivity was seen in lung, kidney, and liver. When ET-1 was infused into the isolated perfused lung of the guinea pig, 64 +/- 1.9% of the label was retained. Subcellular fractionation of the lung homogenate following infusion of labeled ET-1 showed that 93% of the label was associated with membranes and intracellular organelles, suggesting internalization of the bound ET-1. Together, the results indicate a high density of ET-1 binding sites in the lung, liver, and kidney and that these organs may be important in removing circulating ET-1.
内皮素-1（ET-1）已从培养的内皮细胞中分离出来，可能在心血管调节中发挥作用。为了研究标记的ET-1的命运，我们制备了[125I]标记的ET-1（以前的猪和人ET）和ET-3（以前的大鼠ET）。将约0.2微居里（0.2皮摩尔）注入麻醉大鼠的左心室，并分析血样中的放射性长达40分钟。然后处死动物，测定各器官中的放射性分布。ET-1和ET-3均迅速从循环中清除，超过60%的清除发生在第一分钟。ET-1的清除比ET-3稍快。在肺、肾和肝脏中观察到放射性摄取最高。当将ET-1注入豚鼠的离体灌流肺中时，64±1.9%的标记物被保留。注入标记的ET-1后对肺匀浆进行亚细胞分级分离显示，93%的标记物与膜和细胞内细胞器相关，提示结合的ET-1发生了内化。总之，结果表明肺、肝和肾中ET-1结合位点密度高，这些器官可能在清除循环中的ET-1方面很重要。
