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

Vasoactive Intestinal Polypeptide (VIP) interacts with a high affinity to two subclasses of G protein coupled receptors named VPAC1 and VPAC2, and has a 3–10 fold preference for VPAC1 over VPAC2 receptors. Selective ligands for each receptor subclass were recently described. [R16]‐PACAP (1–23) and [...

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Bibliographic Details
Published in:	British journal of pharmacology Vol. 130; no. 4; pp. 819 - 826
Main Authors:	Van Rampelbergh, Jean, Juarranz, Maria‐Guillerma, Perret, Jason, Bondue, Antoine, Solano, Rosa Maria, Delporte, Christine, De Neef, Philippe, Robberecht, Patrick, Waelbroeck, Magali
Format:	Journal Article
Language:	English
Published:	Oxford, UK Blackwell Publishing Ltd 01-06-2000 Nature Publishing
Subjects:	Biological and medical sciences Cell receptors Cell structures and functions Fundamental and applied biological sciences. Psychology Miscellaneous Molecular and cellular biology peptide binding domains Vasoactive intestinal peptide VPAC1 receptors VPAC1‐selective agonists VPAC2 receptors Human Transmembrane protein Agonist Molecular interaction Selectivity In vitro Structure function relationship C terminal-Sequence Transfection Established cell line N terminal-Sequence Vasoactive intestinal peptide Peptidergic receptor G protein
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Summary:	Vasoactive Intestinal Polypeptide (VIP) interacts with a high affinity to two subclasses of G protein coupled receptors named VPAC1 and VPAC2, and has a 3–10 fold preference for VPAC1 over VPAC2 receptors. Selective ligands for each receptor subclass were recently described. [R16]‐PACAP (1–23) and [L22]‐VIP are two selective VPAC1 agonists. Chimaeric human VPAC2‐VPAC1 recombinant receptors expressed in CHO cells were used to identify the receptor domains implicated in these two selective ligands recognition. The VPAC2 preference for [R16]‐PACAP (1–27) over [R16]‐PACAP (1–23) did not require the receptor's NH2‐terminus domain but involved the whole transmembrane domain. In contrast, the selectivity of [L22]‐VIP depended only on the presence of the NH2 terminus and EC2 domains of the VPAC1 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. British Journal of Pharmacology (2000) 130, 819–826; doi:10.1038/sj.bjp.0703384
Bibliography:	J Van Rampelbergh and M‐G Juarranz contributed equally to this work. J Van Rampelbergh and M-G Juarranz contributed equally to this work.
ISSN:	0007-1188 1476-5381
DOI:	10.1038/sj.bjp.0703384