Pharmacological characterization of the mouse NPFF2 receptor.
This study presents the binding and functional properties of the mouse NPFF(2) (mNPFF(2)) receptor, in comparison with its human counterpart (hNPFF(2)). Binding experiments were performed by using the NPFF(2) selective radioligand [(3)H]-EYF in membranes from CHO cells transfected with mouse and human NPFF(2) receptors and compared to membranes from mouse olfactory bulb, the brain region expressing the highest density of NPFF(2) receptors in mouse. mNPFF(2) receptors exhibited a high affinity (Kd=0.2-0.4 nM) for [(3)H]-EYF, comparable to that of hNPFF(2) receptors. Also, the binding selectivity profile of mNPFF(2) receptors was comparable to that of hNPFF(2) receptors, except for three ligands (NPSF, NPVF, RF9) that were about tenfold more potent and active on mouse receptors than on human receptors. In particular, compared to hNPFF(2) receptors, mNPFF(2) receptors were less discriminative towards the proNPFF(B)-derived peptide. This suggests some species-related differences in the binding properties of NPFF(2) receptors that could have repercussion when evaluating the pharmacological properties of drugs in vivo.
Talmont
Franck
F
CNRS/IPBS (Institut de Pharmacologie et Biologie Structurale), 205 route de Narbonne, 31077 Toulouse Cedex, France.
Moulédous
Lionel
L
Piedra-Garcia
Laura
L
Schmitt
Martine
M
Bihel
Frédéric
F
Bourguignon
Jean-Jacques
JJ
Zajac
Jean-Marie
JM
Mollereau
Catherine
C
D000218:Adamantane / Q000031:analogs & derivatives / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D005576:Colforsin / Q000494:pharmacology; D006224:Cricetinae; D003412:Cricetulus; D000242:Cyclic AMP / Q000494:pharmacology; D004151:Dipeptides / Q000378:metabolism; D006801:Humans; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism* / Q000494:pharmacology; D009830:Olfactory Bulb / Q000378:metabolism; D009842:Oligopeptides / Q000378:metabolism; D011485:Protein Binding; D021382:Protein Sorting Signals / Q000235:genetics; D018013:Receptors, Neuropeptide / Q000819:agonists / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction / Q000187:drug effects; D014162:Transfection
D004151:Dipeptides; D009479:Neuropeptides; D009842:Oligopeptides; D021382:Protein Sorting Signals; D018013:Receptors, Neuropeptide; C508361:adamantylcarbonyl-arginyl-phenylalaninamide; C083929:neuropeptide FF receptor; C503959:neuropeptide VF; D005576:Colforsin; C053651:phenylalanyl-leucyl-phenylalanyl-glutaminyl-prolyl-glutaminyl-arginyl-phenylalaninamide; D000242:Cyclic AMP; D000218:Adamantane