Open AccessVasoactive intestinal polypeptide VPAC 1 and VPAC 2 receptor chimeras identify domains responsible for the specificity of ligand binding and activation
Author(s) -
Juarranz Maria G.,
Van Rampelbergh Jean,
Gourlet Philippe,
De Neef Phillippe,
Cnudde Johnny,
Robberecht Patrick,
Waelbroeck Magali
Publication year - 1999
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1046/j.1432-1327.1999.00769.x
Subject(s) - receptor , agonist , vasoactive intestinal peptide , extracellular , chemistry , functional selectivity , endocrinology , medicine , antagonist , enzyme linked receptor , receptor antagonist , biology , biochemistry , neuropeptide
In order to identify the receptor domains responsible for the VPAC 1 selectivity of the VIP 1 agonist, [Lys15, Arg16, Leu27] VIP (1–7)/GRF (8–27) and VIP 1 antagonist, Ac His1 [D‐Phe2, Lys15, Arg16, Leu27] VIP (3–7)/GRF (8–27), we evaluated their binding and functional properties on chimeric VPAC 1 /VPAC 2 receptors. Our results suggest that the N‐terminal extracellular domain is responsible for the selectivity of the VIP 1 antagonist. Selective recognition of the VIP 1 agonist was supported by a larger receptor area: in addition to the N‐terminal domain, the first extracellular loop, as well as additional determinants in the distal part of the VPAC 1 receptor were involved. Furthermore, these additional domains were critical for an efficient receptor activation, as replacement of EC 1 in VPAC 1 by its counter part in the VPAC 2 receptor markedly reduced the maximal response.