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

Abstract

The kinetics of the reactions of 9 opioid peptides with the neutral endopeptidase (enkephalinase) activities of human kidney, rat kidney and rat brain were determined. These opioid peptides can be divided into 2 classes, those that are good inhibitors of Leu5-enkephalin hydrolysis (Ki < 75 .mu.M) and good substrates for the enzyme, and those that are poor inhibitors (Ki > 500 .mu.M) and are not substrates for the enzyme. The former group includes Leu5-enkephalin, Met5-enkephalin, Met5-enkephalin-Arg6-Phe7, .beta.-lipotropin61-69 and .gamma.-endorphin, while the nonreactive opioid peptides include .alpha.-neo-endorphin, .beta.-neo-endorphin, dynorphin1-13 and .beta.-endorphin. 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.