Dynorphin regulates the phagocytic activity of splenic phagocytes in wall lizards: involvement of a κ-opioid receptor-coupled adenylate-cyclase–cAMP–PKA pathway

Abstract

SUMMARY This in vitro study of the wall lizard Hemidactylus flaviviridis demonstrates the role of the opioid peptide dynorphin A(1–17) [dyn A(1–17)] in the regulation of the phagocytic activity of splenic phagocytes. Dyn A(1–17) in a concentration-dependent manner inhibited the phagocytic activity, and the maximum inhibition was recorded at a concentration of 10–9 mol l–1. To explore the receptor-mediated effect of dyn A(1–17), cells were treated simultaneously with the non-selective opioid receptor blocker naltrexone and dyn A(1–17). Naltrexone completely blocked the inhibitory effect of dyn A(1–17) on phagocytosis. Moreover, the involvement of selective opioid receptors was investigated using selective opioid receptor antagonists. CTAP and naltrindole, selective μ- and δ-opioid receptor blockers, respectively, failed to block the inhibitory effect of dyn A(1–17) on phagocytosis. However, the selective κ-opioid receptor blocker NorBNI completely antagonized the inhibitory effect of dyn A(1–17). Regarding the κ-opioid receptor-coupled downstream signaling cascade, the adenylate cyclase (AC) inhibitor SQ 22536 and protein kinase A (PKA) inhibitor H-89 decreased the inhibitory effect of dyn A(1–17) on phagocytosis. Furthermore, treatment with dyn A(1–17) caused an increase in intracellular cAMP content in splenic phagocytes. Thus, it can be concluded that, in H. flaviviridis, dyn A(1–17) negatively regulates the phagocytic activity of splenic phagocytes by acting through κ-opioid receptors that are coupled with the AC–cAMP–PKA signal transduction mechanism.