Vasoactive intestinal polypeptide VPAC(1) and VPAC(2) receptor chimeras identify domains responsible for the specificity of ligand binding and activation
Mg. Juarranz et al., Vasoactive intestinal polypeptide VPAC(1) and VPAC(2) receptor chimeras identify domains responsible for the specificity of ligand binding and activation, EUR J BIOCH, 265(1), 1999, pp. 449-456
In order to identify the receptor domains responsible for the VPAC(1) selec
tivity of the VIP1 agonist, [Lys15, Arg16, Leu27] VIP (1-7)/GRF (8-27) and
VIP1 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 do
main is responsible for the selectivity of the VIP1 antagonist. Selective r
ecognition of the VIP1 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 in
volved. Furthermore, these additional domains were critical for an efficien
t receptor activation, as replacement of EC1 in VPAC(1) by its counter part
in the VPAC(2) receptor markedly reduced the maximal response.