Chen Jin-Chung, Lee Wei-Hsin, Chen Pei-Chun, Tseng Ching-Ping, Huang Eagle Yi-Kung
Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, Chang-Gung University, 259 Wen-Hwa 1st Road, Tao-Yuan, Kwei-Shan, 333, Taiwan, ROC.
Peptides. 2006 May;27(5):1005-14. doi: 10.1016/j.peptides.2005.09.018. Epub 2006 Feb 20.
Neuropeptide FF (NPFF) participates in many physiological functions associated with opioids in the mammalian CNS. We established a pheochromocytoma PC-12 cell line clone stably expressing rat NPFF1 receptors. Both NPFF and FMRFamide activated NPFF1 receptors to couple with Gi/o protein and inhibited adenylyl cyclase activity in PC-12/rNPFF1 cells, but there were no effects on MAPKs (ERK1/2 and p38 MAPK) or PI3K/Akt pathway. FMRFamide also inhibited DARPP-32/Thr34 phosphorylation in the presence of forskolin. Similarly, PFR(Tic)amide, a 'super-agonist' of NPFF receptors, inhibited the production of cAMP and slightly decreased DARPP-32/Thr34 phosphorylation in PC-12/rNPFF1 cells. Intracerebroventricular injections of PFR(Tic)amide blocked behavioral sensitization of locomotor activity to amphetamine, and intrathecal injection of PFR(Tic)amide caused a dose-dependent antinociception in vivo in rats. Thus, "over-activation" of NPFF receptors by PFR(Tic)amide induced different bio-effects from those induced by NPFF in vivo.
神经肽FF（NPFF）参与哺乳动物中枢神经系统中许多与阿片类物质相关的生理功能。我们建立了一个稳定表达大鼠NPFF1受体的嗜铬细胞瘤PC-12细胞系克隆。NPFF和FMRF酰胺均激活NPFF1受体以与Gi/o蛋白偶联，并抑制PC-12/rNPFF1细胞中的腺苷酸环化酶活性，但对丝裂原活化蛋白激酶（ERK1/2和p38 MAPK）或PI3K/Akt信号通路没有影响。在存在福斯高林的情况下，FMRF酰胺也抑制DARPP-32/Thr34磷酸化。同样，NPFF受体的“超级激动剂”PFR(Tic)酰胺抑制PC-12/rNPFF1细胞中cAMP的产生，并略微降低DARPP-32/Thr34磷酸化。脑室内注射PFR(Tic)酰胺可阻断运动活性对苯丙胺的行为敏化，鞘内注射PFR(Tic)酰胺可在大鼠体内引起剂量依赖性的镇痛作用。因此，PFR(Tic)酰胺对NPFF受体的“过度激活”在体内诱导出与NPFF诱导的不同生物效应。
