MolPharm

Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
QUICK SEARCH:   [advanced]


     

This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Submit a response
Right arrow Alert me when this article is cited
Right arrow Alert me when eLetters are posted
Right arrow Alert me if a correction is posted
Services
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Sagan, S.
Right arrow Articles by Lavielle, S.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Sagan, S.
Right arrow Articles by Lavielle, S.

0026-895X/97/010120-08$3.00/0
Copyright © by The American Society for Pharmacology and Experimental Therapeutics
All rights of reproduction in any form reserved.
MOLECULAR PHARMACOLOGY 52:120-127 (1997).

High Affinity Binding of [3H]Propionyl-[Met(O2)11]Substance P(7-11), a Tritiated Septide-Like Peptide, in Chinese Hamster Ovary Cells Expressing Human Neurokinin-1 Receptors and in Rat Submandibular Glands

Sandrine Sagan, Jean-Claude Beaujouan, Yvette Torrens, Monique Saffroy, Gérard Chassaing, Jacques Glowinski, and Solange Lavielle

Laboratoire de Chimie Organique Biologique, URA CNRS 493, Université Pierre et Marie Curie, 75252 Paris Cedex 05, France (S.S., G.C., S.L.), and Chaire de Neuropharmacologie, Institut National de la Santé et de la Recherche Médicale U114, Collège de France, 75005 Paris, France (J.-C.B., Y.T., M.S., J.G.)

Propionyl-[Met(O2)11]substance P(7-11) [ALIE-124 or propionyl-[Met(O2)11]SP(7-11)] has been designed as a septide-like ligand adequate for tritiation and, therefore, adequate for binding studies. In Chinese hamster ovary (CHO) cells expressing human tachykinin neurokinin (NK)-1 receptors, ALIE-124 displaced [3H][Pro9]substance P (SP) from its binding site at micromolar concentrations. However, ALIE-124 stimulated phosphatidylinositol hydrolysis, as previously shown for septide-like peptides. With [3H]ALIE-124 (95 Ci/mmol), we have been able to reveal a high affinity binding site in CHO cells (Kd = 6.6 ± 1.0 nM), with a low maximal binding capacity. [3H]ALIE-124 specific maximal binding represented only 15-20% of that observed with [3H][Pro9]SP in CHO cells. Septide-like peptides, including septide and NKA, were potent competitors (in the nanomolar range) of [3H]ALIE-124 specific binding site. Interestingly, SP and [Pro9]SP were also potent competitors, with 10-fold greater potency for sites labeled with [3H]ALIE-124 than for sites labeled with [3H][Pro9]SP. The NK-1 antagonist RP 67580 also showed a higher potency for [3H]ALIE-124 than for [3H][Pro9]SP-specific binding sites. NKB and [Lys5,methyl-Leu9,Nle10]NKA(4-10) displaced [3H]ALIE-124 binding but with lower potency, whereas senktide had no affinity. The existence of [3H]ALIE-124 specific binding sites was also demonstrated in rat submandibular gland. In this tissue, [3H]ALIE-124 specific maximal binding was higher, reaching 40-50% of that achieved with [3H][Pro9]SP.

Copyright © by The American Society for Pharmacology and Experimental Therapeutics


This article has been cited by other articles:


Home page
 Mol. Pharmacol.Home page
M. M. Rosenkilde, R. David, I. Oerlecke, T. Benned-Jensen, U. Geumann, A. G. Beck-Sickinger, and T. W. Schwartz
Conformational Constraining of Inactive and Active States of a Seven Transmembrane Receptor by Metal Ion Site Engineering in the Extracellular End of Transmembrane Segment V
Mol. Pharmacol., December 1, 2006; 70(6): 1892 - 1901.
[Abstract] [Full Text] [PDF]

Home page
 J. Pharmacol. Exp. Ther.Home page
M. A. Simmons
Functional Selectivity of NK1 Receptor Signaling: Peptide Agonists Can Preferentially Produce Receptor Activation or Desensitization
J. Pharmacol. Exp. Ther., November 1, 2006; 319(2): 907 - 913.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
A. M. Shafer, V. J. Bennett, P. Kim, and J. C. Voss
Probing the Binding Pocket and Endocytosis of a G Protein-coupled Receptor in Live Cells Reported by a Spin-labeled Substance P Agonist
J. Biol. Chem., September 5, 2003; 278(36): 34203 - 34210.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
L. Martini, H. Hastrup, B. Holst, A. Fraile-Ramos, M. Marsh, and T. W. Schwartz
NK1 Receptor Fused to beta -Arrestin Displays a Single-Component, High-Affinity Molecular Phenotype
Mol. Pharmacol., July 1, 2002; 62(1): 30 - 37.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
O. Lequin, G. Bolbach, F. Frank, O. Convert, S. Girault-Lagrange, G. Chassaing, S. Lavielle, and S. Sagan
Involvement of the Second Extracellular Loop (E2) of the Neurokinin-1 Receptor in the Binding of Substance P. PHOTOAFFINITY LABELING AND MODELING STUDIES
J. Biol. Chem., June 14, 2002; 277(25): 22386 - 22394.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
G. Pineyro, M. Azzi, A. De Lean, P. Schiller, and M. Bouvier
Short-Term Inverse-Agonist Treatment Induces Reciprocal Changes in delta -Opioid Agonist and Inverse-Agonist Binding Capacity
Mol. Pharmacol., October 1, 2001; 60(4): 816 - 827.
[Abstract] [Full Text] [PDF]

Home page
 Mol. Pharmacol.Home page
M. M. Rosenkilde and T. W. Schwartz
Potency of Ligands Correlates with Affinity Measured against Agonist and Inverse Agonists but Not against Neutral Ligand in Constitutively Active Chemokine Receptor
Mol. Pharmacol., March 1, 2000; 57(3): 602 - 609.
[Abstract] [Full Text]

Home page
 J. Biol. Chem.Home page
S. Sagan, P. Karoyan, G. Chassaing, and S. Lavielle
Further Delineation of the Two Binding Sites (R*n) Associated with Tachykinin Neurokinin-1 Receptors Using [3-Prolinomethionine11]SP Analogues
J. Biol. Chem., August 20, 1999; 274(34): 23770 - 23776.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. M. Rosenkilde, T. N. Kledal, H. Brauner-Osborne, and T. W. Schwartz
Agonists and Inverse Agonists for the Herpesvirus 8-encoded Constitutively Active Seven-transmembrane Oncogene Product, ORF-74
J. Biol. Chem., January 8, 1999; 274(2): 956 - 961.
[Abstract] [Full Text] [PDF]

Home page
 J. Biol. Chem.Home page
M. Pellegrini, A. A. Bremer, A. L. Ulfers, N. D. Boyd, and D. F. Mierke
Molecular Characterization of the Substance P{middle dot}Neurokinin-1 Receptor Complex. DEVELOPMENT OF AN EXPERIMENTALLY BASED MODEL
J. Biol. Chem., June 15, 2001; 276(25): 22862 - 22867.
[Abstract] [Full Text] [PDF]


Home Help [Feedback] [For Subscribers] [Archive] [Search] [Contents]
All ASPET Journals Molecular Pharmacology Pharmacological Reviews
Molecular Interventions Drug Metabolism and Disposition

Copyright © 1997 by the American Society for Pharmacology and Experimental Therapeutics