title: Dynorphin regulates the phagocytic activity of splenic phagocytes in wall lizards: involvement of a 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) 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.
authors: Department of Zoology, University of Delhi, Delhi, India.
authors: Sunil
authors: S
authors: Kumar
authors: Umesh
authors: U
authors: Rai
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism; D000818:Animals; D002478:Cells, Cultured; D000242:Cyclic AMP / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism; D004399:Dynorphins / Q000378:metabolism*; D008116:Lizards / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D010586:Phagocytes / Q000166:cytology* / Q000378:metabolism; D010587:Phagocytosis; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction; D013154:Spleen / Q000166:cytology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D018377:Neurotransmitter Agents; D017473:Receptors, Opioid, kappa; D004399:Dynorphins; D000242:Cyclic AMP; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases