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Characterization of a novel VPAC1 selective agonist and identification of the receptor domains implicated in the carboxyl-terminal peptide recognition

par Van Rampelbergh, Jean ;Juarranz Moratilla, Maria Guillerma ;Perret, Jason ;Bondue, Antoine ;Solano Haro, Rosa ;Delporte, Christine ;De Neef, Philippe ;Robberecht, Patrick ;Waelbroeck, Magali
Référence British Journal of Pharmacology, 130, 4, page (819-826)
Publication Publié, 2000-06

Article révisé par les pairs

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Résumé :

Vasoactive Intestinal Polypeptide (VIP) interacts with a high affinity to two subclasses of G protein coupled receptors named VPAC(1) and VPAC(2), and has a 3 - 10 fold preference for VPAC(1) over VPAC(2) receptors. Selective ligands for each receptor subclass were recently described. [R(16)]-PACAP (1 - 23) and [L(22)]-VIP are two selective VPAC(1) agonists. Chimaeric human VPAC(2)-VPAC(1) recombinant receptors expressed in CHO cells were used to identify the receptor domains implicated in these two selective ligands recognition. The VPAC(2) preference for [R(16)]-PACAP (1 - 27) over [R(16)]-PACAP (1 - 23) did not require the receptor's NH(2)-terminus domain but involved the whole transmembrane domain. In contrast, the selectivity of [L(22)]-VIP depended only on the presence of the NH(2) terminus and EC(2) domains of the VPAC(1) receptor. The present data support the idea that in the GPCR-B family of receptors the different selective ligands require different domains for their selectivity, and that the peptides carboxyl terminal sequence (amino acids 24 - 27) folds back on the transmembrane receptor domain, close to the peptides, aminoterminus.