Development of the drug which prevents the induction of acute renal failure and its clinical application

本研究旨在阐明内毒素(ET)及其受体在急性肾功能衰竭发生发展中的作用，并开发抑制ET作用的急性肾功能衰竭的预防药物。ET3在肾脏几乎所有部位都有表达，提示其在肾功能中起重要作用(参考文献1)。集合性导管细胞产生ET1受到多种刺激，如高渗(参考文献2)。ET3刺激肾小球系膜细胞合成NO，进而刺激cGMP的产生。这些事件证实了ET在调节肾功能中的重要性。基于这些发现，我们试图提高针对ET受体(主要是ETA受体)的抗体，以抑制ET的作用。我们用几种不同的方法免疫兔子，获得了一些抗体。然而，这些抗体都没有抑制ET在肾功能中的作用，尽管它们中的一些识别了受体。通常情况下，获得良好的疏水激素受体抗体是非常困难的。我们应该进一步尝试获得良好的抗体，但也可以考虑其他方法。

In this research, we intended t o clarify the role of entothelins (ET) and their receptors in the progression of acute renal failure, and to develop the priventive drug for acute renal failure which inhibits the action of ET.The research has been performed well in respect of clarifying the role of ET in acute renal failure. ET3 is expressed in almost all parts of the kidney, suggesting its important role in kidney function (Ref.1). ET1 production in collectiong duct cells is subjects to many stimulus such as hyperosmolality (Ref.2). ET3 stimulates NO synthesis in glomerular mesangial cells which in turn stimulats cGMP production. These events establish the importance of ET in regulation of kidney functions.Based on these findings we have tried to raise antibodies against ET receptors (mainly, ETA recptor) which inhibits ET action. We immunized rabbits using several different methods, and obtained a number of antibodies. However, none of these antibodies inhibited the action of ET in kidney fuunction, although some of them recongnised the receptors. It is a general rule that obtaining a good antibody for hydrophobic hormone receptor is extremely difficult. We should try further to obtain a good antibody, but alternative approaches may be considered.