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Regulation of Cyclic AMP-Dependent Response Element-Binding Protein (CREB) by the Nociceptin/Orphanin FQ in Human Dopaminergic SH-SY5Y Cells

2002; Elsevier BV; Volume: 291; Issue: 3 Linguagem: Inglês

10.1006/bbrc.2002.6503

1090-2104

Myung‐Sunny Kim, Young‐Pyo Cheong, Hong‐Seob So, Kang‐Min Lee, Yong Son, Chang‐Soo Lee, Jae‐Seung Yun, Raekil Park,

Hypothalamic control of reproductive hormones

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 Ca2+, 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, Ca2+-related signaling implicates in the phosphorylation processes of CREB and MAPK simultaneously.