Vasoactive intestinal polypeptide VPAC 1 and VPAC 2 receptor chimeras identify domains responsible for the specificity of ligand binding and activation

• Published in: European journal of biochemistry Vol. 265; no. 1; pp. 449 - 456
• Main Authors: Juarranz, Maria G., Van Rampelbergh, Jean, Gourlet, Philippe, De Neef, Phillippe, Cnudde, Johnny, Robberecht, Patrick, Waelbroeck, Magali
• Format: Journal Article
• Language: English
• Published: 01.10.1999
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1046/j.1432-1327.1999.00769.x

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.