Functional differences between NPFF1 and NPFF2 receptor coupling: High intrinsic activities of RFamide-related peptides on stimulation of [35S]GTPγS binding

Autor: Gouardères, N, Mazarguil, H., Mollereau, C., Chartrel, N., Leprince, Jérôme, Vaudry, H., Zajac, J-M, Gouardères, C.
Přispěvatelé: Institut de pharmacologie et de biologie structurale (IPBS), Centre National de la Recherche Scientifique (CNRS)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées, Neuroendocrinologie cellulaire et moléculaire, Université de Rouen Normandie (UNIROUEN), Normandie Université (NU)-Normandie Université (NU)-Institut National de la Santé et de la Recherche Médicale (INSERM), Différenciation et communication neuronale et neuroendocrine (DC2N)
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Receptors
Neuropeptide
MESH: Drug Interactions
[SDV.NEU.NB]Life Sciences [q-bio]/Neurons and Cognition [q-bio.NC]/Neurobiology
MESH: Cricetinae
Stimulation
Peptide
[CHIM.THER]Chemical Sciences/Medicinal Chemistry
MESH: Neuropeptides
MESH: Dose-Response Relationship
Drug
0302 clinical medicine
Isotopes
MESH: Cricetulus
Cricetinae
MESH: Radionuclide Imaging
[SDV.BC.IC]Life Sciences [q-bio]/Cellular Biology/Cell Behavior [q-bio.CB]
Drug Interactions
MESH: Animals
Neuropeptide FF
Receptor
chemistry.chemical_classification
0303 health sciences
MESH: Receptors
Neuropeptide
Chinese hamster ovary cell
MESH: GTP-Binding Protein alpha Subunits
GTP-Binding Protein alpha Subunits
Biochemistry
MESH: Guanosine 5'-O-(3-Thiotriphosphate)
Protein Binding
MESH: Isotopes
G protein
CHO Cells
Biology
03 medical and health sciences
Cellular and Molecular Neuroscience
Cricetulus
MESH: CHO Cells
Animals
Humans
MESH: Protein Binding
Radionuclide Imaging
030304 developmental biology
Pharmacology
MESH: Humans
Dose-Response Relationship
Drug
Cell Membrane
Neuropeptides
MESH: Saponins
Saponins
Gtpγs binding
chemistry
Guanosine 5'-O-(3-Thiotriphosphate)
Biophysics
[SDV.SP.PHARMA]Life Sciences [q-bio]/Pharmaceutical sciences/Pharmacology
030217 neurology & neurosurgery
Low sodium
MESH: Cell Membrane
Zdroj: Neuropharmacology
Neuropharmacology, Elsevier, 2007, 52 (2), pp.376-386. ⟨10.1016/j.neuropharm.2006.07.034⟩
ISSN: 0028-3908
DOI: 10.1016/j.neuropharm.2006.07.034⟩
Popis: International audience; By using an optimized [(35)S]GTPgammaS binding assay, the functional activities (potency and efficacy) of peptides belonging to three members of the RFamide family; Neuropeptide FF (NPFF), prolactin-releasing peptide (PrRP) and 26RFamide, were investigated on NPFF(1) and NPFF(2) receptors stably expressed in Chinese Hamster Ovary (CHO) cells. Despite their large differences in affinity and selectivity, all analogues tested behaved as agonists toward NPFF(1) and NPFF(2) receptors. High NaCl concentration in the assay strongly increased the efficacy toward NPFF(2) receptors and augmented differences among agonists. In low sodium conditions, whereas the potencies of agonists correlated with their affinities for NPFF(1) receptors, NPFF(2) receptors exhibited an extraordinary activity since all compounds tested displayed EC(50) values of GTPgammaS binding lower than their K(I) values. Comparisons of functional values between NPFF(1) and NPFF(2) receptors revealed unexpected potent selective NPFF(2) agonists especially for the PLRFamide and the VGRFamide sequences. By using blocker peptides, we also show that Galpha(i3) and Galpha(s) are the main transducers of NPFF(1) receptors while NPFF(2) are probably coupled with Galpha(i2), Galpha(i3), Galpha(o) and Galpha(s) proteins. Our data indicate that NPPF(1) and NPFF(2) receptors are differently coupled to G proteins in CHO cells.
Databáze: OpenAIRE
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