Enkephalin-containing polypeptides are potent inhibitors of enkephalin degradation |
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Authors: | Koon-Sea Hui Maria Hui Miriam Banay-Schwartz Teresita DeGuzman Nicholas Ling Abel Lajtha |
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Institution: | 1. Center for Neurochemistry, Rockland Research Institute, Ward''s Island, NY 10035 USA;2. Laboratories for Neuroendocrinology, The Salk Institute, La Jolla, CA 92138 USA |
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Abstract: | Enkephalin-containing polypeptides derived from pro-enkephalin A, pro-enkephalin B, or pro-opiomelanocortin were inhibitors of enkephalin degradation by aminoenkephalinases purified from cytosol or membranes. Of the peptides, Arg°-Met-enkephalin was the most potent inhibitor for the aminoenkephalinases, with an IC50 of about 0.6 μM, it was more effective than bestatin (IC50=0.8–1.0 μM). This inhibition was partly due to substrate competition. Arg°-Met-enkephalin was hydrolyzed by aminoenkephalinases to form Arg, Tyr, and Gly-Gly-Phe-Met in a substrate-inhibited manner. The hexapeptide also inhibited the breakdown of Arg- and Tyr-β-naphthylamide by the membrane aminoenkephalinase. Since Arg°-Met-enkephalin did not inhibit leucine aminopeptidase, it was a more selective inhibitor than bestatin of Met-enkephalin breakdown by aminopeptidases. Arg°-Met-enkephalin inhibited enkephalin breakdown by synaptosomal plasma membranes but not by brain slices. Our data suggest that in addition to their possible role as opioids, the enkephalin-containing polypeptides may be regulators of enkephalin levels. |
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Keywords: | Peptidase Inhibitor Enkephalin Pro-enkephalin Aminoenkephalinase |
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