[Spinorphin, a new inhibitor of enkephalin-degrading enzymes derived from the bovine spinal cord].

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.