Rat NPFF(1) receptor-mediated signaling: functional comparison of neuropeptide FF (NPFF), FMRFamide and PFR(Tic)amide.
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.
Chen
Jin-Chung
JC
Laboratory of Neuropharmacology, Department of Physiology and Pharmacology, Chang-Gung University, 259 Wen-Hwa 1st Road, Tao-Yuan, Kwei-Shan, 333, Taiwan, ROC.
Lee
Wei-Hsin
WH
Chen
Pei-Chun
PC
Tseng
Ching-Ping
CP
Huang
Eagle Yi-Kung
EY
D000262:Adenylyl Cyclases / Q000378:metabolism; D000661:Amphetamine / Q000494:pharmacology; D000698:Analgesia; D000818:Animals; D005576:Colforsin / Q000494:pharmacology; D051937:Dopamine and cAMP-Regulated Phosphoprotein 32 / Q000378:metabolism; D019835:FMRFamide / Q000494:pharmacology*; D007276:Injections, Intraventricular; D007278:Injections, Spinal; D008297:Male; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects; D009479:Neuropeptides / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D016716:PC12 Cells; D010766:Phosphorylation; D051381:Rats; D017207:Rats, Sprague-Dawley; D018013:Receptors, Neuropeptide / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects*; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
D051937:Dopamine and cAMP-Regulated Phosphoprotein 32; D009479:Neuropeptides; D009842:Oligopeptides; C402062:PFR(Tic)amide; D018013:Receptors, Neuropeptide; D044005:Tetrahydroisoquinolines; C083929:neuropeptide FF receptor; D005576:Colforsin; D019835:FMRFamide; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000661:Amphetamine; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3; D048051:p38 Mitogen-Activated Protein Kinases; D000262:Adenylyl Cyclases