Reaction of Opioid Peptides with Neutral Endopeptidase (‘Enkephalinase”)

Abstract: The kinetics of the reactions of nine opioid peptides with the neutral endopeptidase (“enkephalinase”) activities of human kidney, rat kidney, and rat brain have been determined. These opioid peptides can be divided into two classes, those that are good inhibitors of Leu⁵‐enkephalin hydrolysis (K₁ < 75 μM) and good substrates for the enzyme, and those that are poor inhibitors (K₁ > 500 μM) and are not substrates for the enzyme. The former group includes Leu⁵‐enkephalin, Met⁵‐enkephalin, Met⁵‐enkephalin‐Arg⁶‐Phe⁷, β‐lipotropin₆₁₆₉, and γ‐endorphin, while the nonreactive opioid peptides include α‐neo‐endorphin, β‐neo‐endorphin, dynorphin_1–13, and β‐endorphin. These results suggest that those peptides containing the Met⁵‐enkephalin sequence are more reactive than those containing the Leu⁵‐enkephalin sequence. The lack of specificity of this neutral endopeptidase indicates that it may function in the degradation of a variety of biologically active peptides.