The relevance of intact enkephalin molecule in predominantly δ opioid receptor mediated superoxide anion release

Abstract

The effect of intact enkephalin (MENK) molecule or its metabolite Tyr-Gly-Gly (TGG) as well as the effect of synthetic agonist for opioid receptor subtypes (DADLE and DAGO) on superoxide anion release from human neutrophils has been investigated. In lower MENK concentrations, where MENK alone had no effect on O 2 release, inhibition of enkephalinase by thiorphan significantly increased O 2 production, while in higher concentrations, where MENK alone was effective, inhibition of enkephalinase had no effect. Aminopeptidase inhibition by bestatin did not influence O 2 release from MENK treated PMNs. While MENK predominantly stimulated, TGG suppressed O 2 release. Opioid antagonist naloxone (10 −5 M) abrogated the effect of MENK on 02 release. DADLE (δ receptor agonist) increased O 2 release in 10 −11 M concentration, while DAGO (μ receptor agonist) had no effect in any concentration examined. Enkephalinase inhibition increased O 2 production from DADLE but not from DAGO treated PMNs. It seems, therefore, that free radical production is mainly associated with the δ subtype of the opioid receptor. Also, our observations support the hypothesis that enkephalinase might be the enzyme selectively responsible for regulating effects of enkephalins.