title: In vitro properties of a high affinity selective antagonist of the VIP1 receptor.
abstract: A selective high affinity VIP1 receptor antagonist [Acetyl-His1, D-Phe2, Lys15, Arg16, Leu17] VIP(3-7)/GRF(8-27) or PG 97-269 was synthesized, by analogy with recently obtained selective VIP1 receptor agonists. The properties of the new peptide were evaluated on Chinese hamster ovary (CHO) cell membranes expressing either the rat VIP1-, rat VIP2- or the human VIP2-recombinant receptors and on LoVo cell membranes expressing exclusively the human VIP1 receptor. The IC50 values of 125I-VIP binding inhibition by PG 97-269 were 10, 2000, 2 and 3000 nM on the rat VIP1-, rat VIP2-, human VIP1- and human VIP2 receptors, respectively. PG 97-269 had a negligible affinity for the PACAP I receptor type. It did not stimulate adenylate cyclase activity, but inhibited competitively effect of VIP on the VIP1 receptor mediated stimulation of adenylate cyclase activity. The Ki values were respectively of 15 +/- 5 nM and 2 +/- 1 nM for the rat and human VIP1 receptors. Thus the described molecule in the first reported VIP antagonist with an affinity in the nM range and with a high selectivity for the VIP1 receptor subclass. It may be useful for evaluation of the physiological role of VIP in rat and human tissues.
authors.affiliation: Department of Biochemistry and Nutrition, Medical School, Université Libre de Bruxelles, Belgium.
authors.forename: P
authors.initials: P
authors.lastname: Gourlet
authors.forename: P
authors.initials: P
authors.lastname: De Neef
authors.forename: J
authors.initials: J
authors.lastname: Cnudde
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D002462:Cell Membrane / Q000378:metabolism; D006224:Cricetinae; D006801:Humans; D007457:Iodine Radioisotopes; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D018005:Receptors, Vasoactive Intestinal Peptide / Q000037:antagonists & inhibitors*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011994:Recombinant Proteins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D014660:Vasoactive Intestinal Peptide / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology
chemical_list: D007457:Iodine Radioisotopes; C110307:PG 97-269; D010446:Peptide Fragments; D010455:Peptides; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011994:Recombinant Proteins; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases