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

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 O2- release, inhibition of enkephalinase by thiorphan significantly increased O2- production, while in higher concentrations, where MENK alone was effective, inhibition of enkephalinase had no effect. Aminopeptidase inhibition by bestatin did not influence O2- release from MENK treated PMNs. While MENK predominantly stimulated, TGG suppressed O2- release. Opioid antagonist naloxone (10(-5) M) abrogated the effect of MENK on O2- release. DADLE (delta receptor agonist) increased O2- release in 10(-11) M concentration, while DAGO (mu receptor agonist) had no effect in any concentration examined. Enkephalinase inhibition increased O2- production from DADLE but not from DAGO treated PMNs. It seems, therefore, that free radical production is mainly associated with the delta subtype of the opioid receptor. Also, our observations support the hypothesis that enkephalinase might be the enzyme selectively responsible for regulating effects of enkephalins.