DEGRADATION AND OXIDATION OF METHIONINE ENKEPHALIN BY HUMAN-NEUTROPHILS

Abstract

Met5-enkephalin, Tyr-Gly-Gly-Phe-Met, is an endogenous pentapeptide, with morphine agonist activity. This study demonstrated that Met5-enkephalin was degraded with the release of tyrosine by resting human PMN [neutrophil], whereas it was degraded as well as oxidized to its sulfoxide derivative, Met5-(O)-enkephalin, by phagocytosing PMN. PMN also degraded Met5-(O)-enkephalin but to a lesser extent. Bacitracin at 1 gm/l inhibited the degradation and oxidation of Met5-enkephalin without affecting the production of superoxide and the viability of PMN. The oxidation of Met5-enkephalin by phagocytosing PMN was inhibited by catalase or NaN3 but not by superoxide dismutase. This suggests that the oxidation of Met5-enkephalin by phagocytosing PMN was, at least in part, dependent on the MPO system (MPO-H2O2-halide). Using purified canine MPO, it was further demonstrated that MPO-H2O2-Cl- oxidized Met5-enkephalin to Met5-(O)-enkephalin. The MPO-mediated oxidation of Met5-enkephalin was inhibited by methionine but not by methionine sulfoxide, tyrosine, glycine or phenylalanine, confirming that it was the methionine moiety of Met5-enkephalin which was oxidized. Since both the sulfoxide derivative and the degradation products of Met5-enkephalin have reduced opiate agonist activity, oxidation and degradation of Met5-enkephalin by PMN may contribute to the pain at the site of inflammation.