Naloxone is an inappropriate antagonist of met-enkephalin-modulated superoxide anion release

Abstract

Met-enkephalin (MENK) increased superoxide anion release by human polymorphonuclear cells (PMNs) at a physiological (10(-10) M) concentration and decreased release at a relatively high (10(-8) M) concentration. Surprisingly, naloxone (NAL), used as a specific antagonist in these experiments, displayed immunomodulatory actions of its own, increasing superoxide anion release at 10(-10) and 10(-8) M concentrations. Although both were effective, the dose-response curves were different for NAL and MENK. NAL and MENK also had a combined influence on O2- release. The stimulative effect of 10(-10) M MENK could be abolished by 10(-8) M NAL in seven of eight cases. Unexpectedly, the stimulatory effect of 10(-8) and 10(-10) M NAL could be abrogated by MENK in five of eight cases as well. The fact that NAL and MENK mutually interfere with one another in their effect upon O2- release by human PMNs discredits NAL as an appropriate antagonist in this system.