Methionine-enkephalin stimulates hydrogen peroxide and nitric oxide production in rat peritoneal macrophages: Interaction of mu, delta and kappa opioid receptors

Abstract

Objective: Methionine-enkephalin ( MET) modulates various functions of macrophages related to both immune and inflammatory reactions in a naloxone reversible manner, suggesting that opioid receptors are involved in the regulation of macrophage activity. Since an endogenous opioid ligand might interact with more than one type of opioid receptor, the receptor interaction determines its effect on a particular function. Methods: In the present study we have investigated the involvement of different opioid receptor types/subtypes in MET-induced modulation of H2O2 and NO production in macrophages. Thioglycollate-elicited or resident rat peritoneal macrophages were treated in vitro with MET and/or specific antagonists of delta(1,2), delta(1), delta(2), mu and kappa opioid receptors. Results: MET increased H2O2 production in phorbol myristate acetate-stimulated rat peritoneal macrophages mainly through delta(1) opioid receptor. MET also enhanced NO production in rat peritoneal macrophages stimulated with lipopolysaccharide through delta(1) and mu opioid receptors. The blockade of mu and kappa receptor facilitated a potentiating effect of MET on H2O2 release, and blockade of kappa receptor further raised the MET-induced increase of NO production in macrophages. Conclusion: It is concluded that both negative and positive functional interaction between delta, mu and kappa opioid receptors regulate the influence of MET on H2O2 and NO production in rat peritoneal macrophages. Copyright (C) 2004 S. Karger AG, Basel.