Abstract
CONSIDERABLE evidence now exists to suggest that the endogenous opioid pentapeptides Met-enkephalin (Tyr-Gly-Gly-Phe-Met) and Leu-enkephalin (Tyr-Gly-Gly-Phe-Leu) function as neurotransmitters in the central nervous system. A correlate of this hypothesis is that a specific inactivation mechanism must operate in the vicinity of opiate receptors to turn off rapidly the enkephalin signal. Indeed recent studies have shown that the pentapeptides are subject to extremely rapid inactivation in various tissues, occurring primarily by cleavage of the Tyr–Gly amide bond1–5. This feature accounts for the short-lasting biological activity of these peptides, contrasting with the potent activity of synthetic analogues such as (D-Ala2)-Met-enkephalinamide in which this bond is protected6. However, many tissues including brain contain a spectrum of peptidases with low specificities and affinities7 and no evidence has been yet provided for the involvement of a specific enzyme in the regulation of enkephalinergic transmission. We now report the presence of a high-affinity peptidase in a particulate fraction of mouse striatum splitting the Leu-enkephalin molecule with release of a tripeptide fragment (Tyr-Gly-Gly) and exhibiting definite substrate specificity. The marked and selective increase in the activity of this peptidase in the striatum of mice chronically treated with morphine suggests that it might be associated with enkephalinergic transmission.
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MALFROY, B., SWERTS, J., GUYON, A. et al. High-affinity enkephalin-degrading peptidase in brain is increased after morphine. Nature 276, 523–526 (1978). https://doi.org/10.1038/276523a0
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DOI: https://doi.org/10.1038/276523a0
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