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

Abstract

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?moll -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 - opioid receptor blockers, respectively, failed to block the inhibitory effect of dyn A (1-17) on phagocytosis. However, the selective -opioid receptor blocker NorBNI completely antagonized the inhibitory effect of dyn A (1-17). Regarding the -opioid receptorcoupled 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 -opioid receptors that are coupled with the AC-cAMP-PKA signal transduction mechanism. © 2011. Published by The Company of Biologists Ltd.