The effect of opioid peptides on superoxide, anion production in rat peritoneal macrophages stimulated with zymosan: involvement of µ, δ and κ opioid receptors

Abstract

It is well documented that endogenous opioid peptides modulate the activity of immune and inflammatory cells. Opioid peptides exert biological effects through at least three opioid receptor types, known as µ, δ and κ. In the present study we have investigated which types of opioid receptors are involved in the opioid peptide-induced modulation of superoxide an/on release from macrophages. Rat peritoneal macrophages were stimulated with zymosan, and treated in vitro with opioid peptides and/or antagonists specific for different opioid receptor types. The results showed that the µ opioid receptor agonist, beta-endorphin, and the k opioid receptor agonist dynorphin A, decreased superoxide anion production. Conversely methionine-enkephalin (Met-Enk) and leucine-enkephalin, that have a preference for δ opioid receptors, did not affect superoxide anion release. Furthermore, we have tested the effect of Met-Enk on superoxide anion release from macrophages under blockade of all receptors with specific antagonists except for one receptor subtype. Accordingly, it was found that the Met-Enk induced increase and decrease of superoxide anion production were mediated through δ1,2 and µκ opioid receptors, respectively. It can be concluded that opposing activity of µ, and κ receptors vs. δ receptors together with the affinity for a ceflain receptor-type determines the effect of a particular endogenous opioid peptide on superoxide anion release from rat peritoneal macrophages.

Poznato je da endogeni opioidni peptidi modulišu aktivnost imunskih i inflamatornih ćelija. Opioidni peptidi ostvaruju biološke efekte preko tri tipa receptora, µ, δ i κ. U ovom radu ispitivali smo koji tipovi opioidnih receptora učestvuju u opioidnoj modulaciji oslobadanjasuperoksid anjona iz peritonealnih makrofaga. Peritonealne makrofage pacova su stimulisane zimozanom, i tretirane in vitro sa opioidnim peptidima i/ili specifičnim antagonistima različitih tipova opioidnih receptora. Rezultati su pokazali da beta-endorphin, agonist µ, opiodnih receptora, i dynorphin A, agonist κ opiodnih receptora, smanjuju produkciju superoksid anjona. S druge strane metionin-enkefalin (Met-Enk) i leucin-enkefalin, koji se prevashodno vezuju za δ opioidne receptore, nisu uticali na oslobadanje superoksid anjona. Pored toga, ispitivali smo uticaj Met-Enk na oslobađanje superoksid anjona iz makrofaga u uslovima blokade svih receptora sa specifičnim antagonistima izuzev jednog tipa/podtipa opioidnog receptora. Shodno tome pokazali smo da Met-Enk povećava oslobadanje superoksid anjona preko δ1,2 a smanjuje oslobadanje superoksid anjona preko µk opioidnih receptora. Može se zaključiti da je uticaj endogenih opioidnih peptida na oslobadanje superoksid anjona iz peritonealnih makrofaga pacova određen suprotnom aktivnošću (µ i k receptora u odnosu na δ receptore, kao i različitim afinitetom peptida za pojedine tipove opioidnih receptora.