Methionine-Enkephalin Stimulates Hydrogen Peroxide and Nitric Oxide Production in Rat Peritoneal Macrophages: Interaction of μ, δ and κ Opioid Receptors

Abstract

<i>Objective:</i> 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. <i>Methods:</i> In the present study we have investigated the involvement of different opioid receptor types/subtypes in MET-induced modulation of H<sub>2</sub>O<sub>2</sub> and NO production in macrophages. Thioglycollate-elicited or resident rat peritoneal macrophages were treated in vitro with MET and/or specific antagonists of δ<sub>1,2</sub>, δ<sub>1</sub>, δ<sub>2</sub>, µ and ĸ opioid receptors. <i>Results:</i> MET increased H<sub>2</sub>O<sub>2 </sub>production in<sub></sub>phorbol myristate acetate-stimulated rat peritoneal macrophages mainly through δ<sub>1</sub> opioid receptor. MET also enhanced NO<sub></sub>production in rat peritoneal macrophages stimulated with lipopolysaccharide through δ<sub>1</sub> and µ opioid receptors. The blockade of µ and ĸ receptor facilitated a potentiating effect of MET on H<sub>2</sub>O<sub>2</sub> release, and blockade of ĸ receptor further raised the MET-induced increase of NO production in macrophages. <i>Conclusion:</i> It is concluded that both negative and positive functional interaction between δ, µ and ĸ opioid receptors regulate the influence of MET on H<sub>2</sub>O<sub>2</sub> and NO production in rat peritoneal macrophages.