title: Functional properties of Pfr(Tic)amide and BIBP3226 at human neuropeptide FF2 receptors.
abstract: The functional characteristics of two putative neuropeptide FF (NPFF) antagonists, BIBP3226 and PFR(Tic)amide, on the human neuropeptide FF receptor subtype 2 (hNPFF2) were investigated. Surprisingly, PFR(Tic)amide was shown to exhibit agonist properties in the [35S]guanosine-5'-O-(3-thio)triphosphate ([35S]GTPgammaS) binding assay. The efficacy of PFR(Tic)amide was significantly greater than that of (1DMe)Y8Fa, a stable analog of NPFF, and PFR(Tic)amide can therefore be classified as a 'super-agonist'. BIBP3226 did act as a reversible competitive antagonist on the hNPFF2 receptor. However, high concentrations of BIBP3226 also non-specifically increased [35S]GTP-gammaS binding. The usefulness of BIBP3226 as an antagonist tool on the NPFF receptor is thus limited.
authors.affiliation: Juvantia Pharma Ltd, Lemminkäisenkatu 5,. Pharmacity, Turku FIN-20520, Finland. mia.engstrom@juvantia.com
authors.forename: Mia
authors.initials: M
authors.lastname: Engström
authors.forename: Siegfried
authors.initials: S
authors.lastname: Wurster
authors.forename: Juha-Matti
authors.initials: JM
authors.lastname: Savola
authors.forename: Pertti
authors.initials: P
authors.lastname: Panula
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology*; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D006224:Cricetinae; D004072:Digitonin / Q000494:pharmacology; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism; D006801:Humans; D008024:Ligands; D009479:Neuropeptides / Q000494:pharmacology*; D018013:Receptors, Neuropeptide / Q000819:agonists* / Q000037:antagonists & inhibitors*; D011994:Recombinant Proteins / Q000819:agonists / Q000037:antagonists & inhibitors; D012964:Sodium / Q000494:pharmacology; D044005:Tetrahydroisoquinolines / Q000494:pharmacology*
chemical_list: C092926:BIBP 3226; D008024:Ligands; D009479:Neuropeptides; C402062:PFR(Tic)amide; D018013:Receptors, Neuropeptide; D011994:Recombinant Proteins; D044005:Tetrahydroisoquinolines; C083929:neuropeptide FF receptor; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D001120:Arginine; D012964:Sodium; D004072:Digitonin