Lou L G, Zhang Z, Ma L, Pei G
Shanghai Institute of Cell Biology, Chinese Academy of Sciences.
J Neurochem. 1998 Mar;70(3):1316-22. doi: 10.1046/j.1471-4159.1998.70031316.x.
The effect of nociceptin/orphanin FQ (N/OFQ), an endogenous ligand for the newly identified opioid receptor-like (ORL1) receptor, on mitogen-activated protein kinase (MAPK) was investigated in Chinese hamster ovary cells stably expressing ORL1 receptor. N/OFQ rapidly stimulated phosphorylation and activity of MAPK (p42 and p44 isoforms) in a concentration-dependent manner. The p42 isoform was preferentially activated by N/OFQ. Maximal activation (5.4 +/- 1.2-fold of basal for p42 isoform) was achieved after a 1-min exposure of cells to 100 nM N/OFQ. The activation was blocked completely by pretreatment with pertussis toxin, but was not reversed by naloxone. U-73122, a phospholipase C-specific inhibitor, significantly inhibited phospholipase C activity, as well as MAPK activation stimulated by N/OFQ. Furthermore, N/OFQ-stimulated MAPK activation was suppressed by a protein kinase C-specific inhibitor, chelerythrine. The results demonstrate that N/OFQ can effectively stimulate MAPK by the activation of ORL1 receptor and pertussis toxin-sensitive G proteins, and that phospholipase C, as well as protein kinase C, is critically involved in these processes.
在中国仓鼠卵巢细胞中稳定表达阿片受体样（ORL1）受体，研究了新鉴定的阿片受体样受体的内源性配体孤啡肽/孤啡肽FQ（N/OFQ）对丝裂原活化蛋白激酶（MAPK）的影响。N/OFQ以浓度依赖的方式迅速刺激MAPK（p42和p44亚型）的磷酸化和活性。N/OFQ优先激活p42亚型。细胞暴露于100 nM N/OFQ 1分钟后，达到最大激活（p42亚型为基础水平的5.4±1.2倍）。用百日咳毒素预处理可完全阻断该激活，但纳洛酮不能使其逆转。磷脂酶C特异性抑制剂U-73122显著抑制磷脂酶C活性以及N/OFQ刺激的MAPK激活。此外，蛋白激酶C特异性抑制剂白屈菜红碱抑制了N/OFQ刺激的MAPK激活。结果表明，N/OFQ可通过激活ORL1受体和百日咳毒素敏感的G蛋白有效刺激MAPK，且磷脂酶C以及蛋白激酶C在这些过程中起关键作用。
