These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: Spatial proximity between the VPAC1 receptor and the amino terminus of agonist and antagonist peptides reveals distinct sites of interaction.
    Author: Ceraudo E, Hierso R, Tan YV, Murail S, Rouyer-Fessard C, Nicole P, Robert JC, Jamin N, Neumann JM, Robberecht P, Laburthe M, Couvineau A.
    Journal: FASEB J; 2012 May; 26(5):2060-71. PubMed ID: 22291440.
    Abstract:
    Vasoactive intestinal peptide (VIP) plays a major role in pathophysiology. Our previous studies demonstrated that the VIP sequence 6-28 interacts with the N-terminal ectodomain (N-ted) of its receptor, VPAC1. Probes for VIP and receptor antagonist PG97-269 were synthesized with a photolabile residue/Bpa at various positions and used to explore spatial proximity with VPAC1. PG97-269 probes with Bpa at position 0, 6, and 24 behaved as high-affinity receptor antagonists (K(i)=12, 9, and 7 nM, respectively). Photolabeling experiments revealed that the [Bpa(0)]-VIP probe was in physical contact with VPAC1 Q(135), while [Bpa(0)]-PG97-269 was covalently bound to G(62) residue of N-ted, indicating different binding sites. In contrast, photolabeling with [Bpa(6)]- and [Bpa(24)]-PG97-269 showed that the distal domains of PG97-269 interacted with N-ted, as we previously showed for VIP. Substitution with alanine of the K(143), T(144), and T(147) residues located in the first transmembrane domain of VPAC1 induced a loss of receptor affinity (IC(50)=1035, 874, and 2070 nM, respectively), and pharmacological studies using VIP2-28 indicated that these three residues play an important role in VPAC1 interaction with the first histidine residue of VIP. These data demonstrate that VIP and PG97-269 bind to distinct domains of VPAC1.
    [Abstract] [Full Text] [Related] [New Search]