title: Vasoactive intestinal peptide modification at position 22 allows discrimination between receptor subtypes.
abstract: Secretin and growth hormone releasing factor (GRF) have a weak affinity for VIP (vasoactive intestinal peptide)/PACAP (pituitary adenylate cyclase activating polypeptide) receptors, but discriminate between VIP1/PACAP and VIP2/PACAP receptors. This previously allowed us to develop modified secretin and GRF derivatives as high affinity and highly selective VIP1/PACAP receptor ligands. We tested the hypothesis that the presence of a Gln residue at position 24 and a Leu residue at position 22 was responsible for their VIP1/PACAP receptor selectivity. [Gln24]VIP was not different from VIP but [Leu22]VIP had a 100-fold lower affinity for VIP2/PACAP receptors as compared to VIP1/PACAP receptors. The substitution of Tyr22 by Phe22 in VIP had no significant effect on the recognition of both receptors but [Ala22]VIP had a reduced affinity for the VIP2/PACAP receptor. This indicated that an aromatic residue at position 22 of VIP was required for a high affinity for the VIP2/PACAP receptor but not for the VIP1/PACAP receptor.
authors.affiliation: Department of Biochemistry and Nutrition, School of Medicine, Université Libre de Bruxelles, Brussels, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gourlet
authors.forename: M C
authors.initials: MC
authors.lastname: Vandermeers-Piret
authors.forename: J
authors.initials: J
authors.lastname: Rathé
authors.forename: P
authors.initials: P
authors.lastname: De Neef
authors.forename: J
authors.initials: J
authors.lastname: Cnudde
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D006224:Cricetinae; D008566:Membranes / Q000378:metabolism; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism; D010455:Peptides / Q000138:chemical synthesis / Q000737:chemistry; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry* / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives / Q000737:chemistry* / Q000378:metabolism*
chemical_list: D009479:Neuropeptides; D010455:Peptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D014660:Vasoactive Intestinal Peptide