Nishimura K, Hazato T
Department of Anesthesiology, Juntendo University, School of Medicine, Tokyo.
Masui. 1993 Oct;42(10):1497-503.
We have isolated a potent inhibitor of enkephalin-degrading enzymes from the bovine spinal cord, and determined its amino-acid sequence and inhibitory activity against enkephalin-degrading enzymes. This new substance, isolated and identified from the bovine spinal cord, is composed of a heptapeptide (Leu-Val-Val-Tyr-Pro-Trp-Thr). The inhibitory activity (IC50) of this new substance against enkephalin-degrading enzymes, purified from monkey brain, are 3.3 micrograms.ml-1 against aminopeptidase, 1.4 microgram.ml-1 against dipeptidyl aminopeptidase, 2.4 micrograms.ml-1 against angiotensin converting enzyme, and 10 micrograms.ml-1 against enkephalinase. This new substance showed no inhibitory activity against enkephalin-degrading enzymes purified from kidney, blood, etc. According to the above results, this substance is thought to be a new neuromodulator derived from the spinal cord. Because it was derived from the spinal cord, we have named it "Spinorphin". The discovery in the bovine spinal cord of endogenous heptapeptide, Spinorphin, with inhibitory activity on enkephalin-degrading enzymes raises a number of pertinent questions which cannot be adequately dealt with in this study. It will now be possible, however, to test the very hypothesis that this new peptide act as neurotransmitters or neuromodulators at synaptic junctions.
我们从牛脊髓中分离出一种强力脑啡肽降解酶抑制剂，并确定了其氨基酸序列以及对脑啡肽降解酶的抑制活性。这种从牛脊髓中分离并鉴定出的新物质由一种七肽（亮氨酸-缬氨酸-缬氨酸-酪氨酸-脯氨酸-色氨酸-苏氨酸）组成。该新物质对从猴脑中纯化得到的脑啡肽降解酶的抑制活性（IC50）分别为：对氨肽酶为3.3微克/毫升，对二肽基氨肽酶为1.4微克/毫升，对血管紧张素转换酶为2.4微克/毫升，对脑啡肽酶为10微克/毫升。该新物质对从肾脏、血液等中纯化得到的脑啡肽降解酶没有抑制活性。根据上述结果，这种物质被认为是一种源自脊髓的新型神经调节剂。由于它源自脊髓，我们将其命名为“脊髓吗啡肽”。在牛脊髓中发现具有抑制脑啡肽降解酶活性的内源性七肽脊髓吗啡肽引发了许多相关问题，本研究无法充分解决这些问题。然而，现在有可能检验这一新肽在突触连接处作为神经递质或神经调节剂的这一假设。
