title: β-Endorphin inhibits phagocytic activity of lizard splenic phagocytes through μ receptor-coupled adenylate cyclase-protein kinase A signaling pathway.
abstract: The receptor-coupled intracellular signaling mechanism of endogenous opioid peptide β-endorphin (β-end) is explored for the first time in ectothermic vertebrates using wall lizard as a model. β-End inhibited the percentage phagocytosis and phagocytic index of lizard splenic phagocytes in a dose-dependent manner. The inhibitory effect of β-end on phagocytosis was completely antagonized by non-selective opioid receptor antagonist naltrexone and also by selective μ-receptor antagonist CTAP. However, selective antagonists for other opioid receptors like NTI for δ-receptor and NorBNI for κ-receptor did not alter the effect of β-end on phagocytosis. This suggests that β-end mediated its inhibitory effect on phagocytic activity of splenic phagocytes exclusively through μ opioid receptors. The μ opioid receptor-coupled downstream signaling cascade was subsequently explored using inhibitors of adenylate cyclase (SQ 22536) and protein kinase A (H-89). Both SQ 22536 and H-89 abolished the inhibitory effect of β-end on phagocytosis in a concentration-related manner. Implication of cAMP as second messenger was corroborated by cAMP assay where an increase in intracellular cAMP level was observed in response to β-end treatment. It can be concluded that β-end downregulated the phagocytic activity of lizard splenic phagocytes through μ opioid receptor-coupled adenylate cyclase-cAMP-protein kinase A pathway.
authors.affiliation: Department of Zoology, University of Delhi, Delhi 110 007, India.
authors.forename: Sunil
authors.initials: S
authors.lastname: Kumar
authors.forename: Soma M
authors.initials: SM
authors.lastname: Ghorai
authors.forename: Umesh
authors.initials: U
authors.lastname: Rai
mesh_terms: D000225:Adenine / Q000031:analogs & derivatives / Q000494:pharmacology; D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007546:Isoquinolines / Q000494:pharmacology; D008116:Lizards; D009271:Naltrexone / Q000494:pharmacology; D010455:Peptides / Q000494:pharmacology; D010586:Phagocytes / Q000166:cytology / Q000187:drug effects*; D010587:Phagocytosis / Q000187:drug effects*; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013154:Spleen / Q000166:cytology*; D013449:Sulfonamides / Q000494:pharmacology; D001615:beta-Endorphin / Q000494:pharmacology*
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D007546:Isoquinolines; D010455:Peptides; D017450:Receptors, Opioid, mu; D013449:Sulfonamides; C017759:9-(tetrahydro-2-furyl)-adenine; D009271:Naltrexone; D001615:beta-Endorphin; C009862:connective tissue-activating peptide; D017868:Cyclic AMP-Dependent Protein Kinases; D000262:Adenylyl Cyclases; D000225:Adenine; C063509:N-(2-(4-bromocinnamylamino)ethyl)-5-isoquinolinesulfonamide