engleski

The link between met-enkephalin-induced down-regulation of APN activity and release of superoxide anion

We have previously shown that methionine-enkephalin (MENK) differentially alters the production of superoxide anion (O_2^-)from neutrophils of different donors. This effect could be due to variable activity of proteolytic enzymes involved in the degradation of this neuropeptide. In this study, we investigated the possible association between the effect of MENK on O_2^- release and the two neutrophil associated hydrolytic enzymes that participate in enkephalin degradation ; aminopeptidase N (APN) and neutral endopeptidase (NEP). We have demonstrated that APN but not NEP activity was down-regulated by MENK. This might be due to internalization, since APN down-regulation was observed only within intact neutrophils and not with the respective membranes. Preincubation of neutrophils with inhibitory anti CD13 MoAb (WM15) abbrogated the suppresive effect of MENK (10_-12, 10_-10 and 10_-8 M). These facts, show that in the periphery (as well as the brain) the dominant role in MENK hydrolysis can be attributed to APN. Also, they further support the idea of the link between the membrane associated CD13 and binding of the ligand to the opioid receptor.

methionine-enkephalin; superoxide anion; aminopeptidase N; neutrophils

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