title: Regulation of cyclic AMP-dependent response element-binding protein (CREB) by the nociceptin/orphanin FQ in human dopaminergic SH-SY5Y cells.
abstract: Nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for opioid receptor-like (ORL1) receptor, transduces signaling cascades implicated in MAPK, PKC, PLC, and calcium, etc. This study was designed to investigate the intracellular signaling mechanism of N/OFQ in human dopaminergic neuroblastoma SH-SY5Y cells. N/OFQ rapidly induced the phosphorylation of CREB, which was significantly suppressed by pretreatment of PKA inhibitor, but not by MAPK inhibitors. It also time-dependently increased the phosphorylation of MAPK, which was proven as ERKs, whereas it did not affect the PI3K activity. Interestingly, KT5720, a specific inhibitor of PKA, markedly suppressed the phosphorylation of MAPK by N/OFQ in SH-SY5Y cells. Furthermore, BAPTA-AM, an intracellular chelator of Ca(2+), completely abolished the phosphorylation of CREB as well as MAPK in N/OFQ-treated SH-SY5Y cells. Taken together, these results suggest that N/OFQ independently induces the activation of CREB prior to MAPK phosphorylation, which was also modulated by PKA. Furthermore, Ca(2+)-related signaling implicates in the phosphorylation processes of CREB and MAPK simultaneously.
authors.affiliation: Institute of Medical Science, Wonkwang University School of Medicine, Iksan Chonbuk, 570-749, South Korea.
authors.forename: Myung-Sunny
authors.initials: MS
authors.lastname: Kim
authors.forename: Young-Pyo
authors.initials: YP
authors.lastname: Cheong
authors.forename: Hong-Seob
authors.initials: HS
authors.lastname: So
authors.forename: Kang-Min
authors.initials: KM
authors.lastname: Lee
authors.forename: Yong
authors.initials: Y
authors.lastname: Son
authors.forename: Chang-Soo
authors.initials: CS
authors.lastname: Lee
authors.forename: Jae-Seung
authors.initials: JS
authors.lastname: Yun
authors.forename: Raekil
authors.initials: R
authors.lastname: Park
mesh_terms: D002118:Calcium / Q000502:physiology; D002460:Cell Line; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors; D004298:Dopamine / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006801:Humans; D007700:Kinetics; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D009447:Neuroblastoma; D018847:Opioid Peptides / Q000494:pharmacology*; D010766:Phosphorylation; D047428:Protein Kinase Inhibitors; D000097629:Nociceptin
chemical_list: D002118:Calcium; D017362:Cyclic AMP Response Element-Binding Protein; D017868:Cyclic AMP-Dependent Protein Kinases; D004298:Dopamine; D004791:Enzyme Inhibitors; D020928:Mitogen-Activated Protein Kinases; D018847:Opioid Peptides; D047428:Protein Kinase Inhibitors; D000097629:Nociceptin