Functional properties of Pfr(Tic)amide and BIBP3226 at human neuropeptide FF2 receptors.
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.
Engström
Mia
M
Juvantia Pharma Ltd, Lemminkäisenkatu 5,. Pharmacity, Turku FIN-20520, Finland. mia.engstrom@juvantia.com
Wurster
Siegfried
S
Savola
Juha-Matti
JM
Panula
Pertti
P
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*
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