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Characterization of a novel VPAC 1 selective agonist and identification of the receptor domains implicated in the carboxyl‐terminal peptide recognition
Author(s) -
Van Rampelbergh Jean,
Juarranz MariaGuillerma,
Perret Jason,
Bondue Antoine,
Solano Rosa Maria,
Delporte Christine,
De Neef Philippe,
Robberecht Patrick,
Waelbroeck Magali
Publication year - 2000
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0703384
Subject(s) - receptor , agonist , transmembrane domain , g protein coupled receptor , peptide , biology , transmembrane protein , vasoactive intestinal peptide , biochemistry , chemistry , microbiology and biotechnology , neuropeptide
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.British Journal of Pharmacology (2000) 130 , 819–826; doi: 10.1038/sj.bjp.0703384