Schuller M, Stetter R, Skrabal S, Missbichler A, Woloszczuk W, Hartter E
II. Medizinische Universitätsklinik, Vienna, Austria.
Eur J Clin Chem Clin Biochem. 1991 Feb;29(2):147-50.
Endothelin, a potent endogenous vaso-constrictor, is derived from its biosynthetic precursor by proteolytic degradation. The last step cleaves big-endothelin(1-38) to endothelin(1-21) and a C-terminal fragment. We have developed a radioimmunoassay for this peptide, based on an antiserum recognizing the C-terminal sequence big-endothelin(22-38) and cross-reacting with intact big-endothelin. To test for the presence of immunoreactive big-endothelin(22-38) in plasma, samples were extracted by passage through C18 silica cartridges, and desorption with methanol/water volume fraction 0.8. The yields of this purification and concentration procedure were about 70%. In 15 healthy persons we found concentrations of 1-11 pmol/l, which is about 10-fold higher than the reference levels reported for endothelin(1-21) or big-endothelin(1-38). Thus, endothelin-derived peptides containing the big-endothelin(22-38) sequence, but different from intact big-endothelin, do circulate in human blood. If a sufficiently tight correlation to levels of circulating endothelin(2-21) can be proven, this would facilitate studies on the physiological role of endogenous endothelin.
内皮素是一种强大的内源性血管收缩剂，由其生物合成前体经蛋白水解降解产生。最后一步将大内皮素（1-38）裂解为内皮素（1-21）和一个C末端片段。我们基于一种识别C末端序列大内皮素（22-38）并与完整大内皮素发生交叉反应的抗血清，开发了一种针对该肽的放射免疫测定法。为检测血浆中免疫反应性大内皮素（22-38）的存在，样本通过C18硅胶柱进行萃取，并用体积分数为0.8的甲醇/水进行解吸。该纯化和浓缩程序的回收率约为70%。在15名健康个体中，我们发现其浓度为1-11 pmol/L，这大约比报道的内皮素（1-21）或大内皮素（1-38）的参考水平高10倍。因此，含有大内皮素（22-38）序列但不同于完整大内皮素的内皮素衍生肽确实在人体血液中循环。如果能够证明其与循环内皮素（2-21）水平存在足够紧密的相关性，这将有助于对内源性内皮素的生理作用进行研究。
