title: The C-terminus ends of secretin and VIP interact with the N-terminal domains of their receptors.
abstract: C-terminally truncated secretin and VIP molecules were synthesized, and their ability to occupy the recombinant secretin and VIP1 receptors stably expressed in Chinese hamster ovary (CHO) cells and to stimulate adenylate cyclase activity was studied. On secretin receptors, secretin (1-26) and secretin (1-24) were 10- and 50-fold less potent but as efficient as secretin (1-27); VIP (1-27) was as potent and efficient as VIP (1-28), and VIP (1-26) and VIP (1-25) were both 100-fold less potent. On VIP1 receptor, VIP (1-28) and VIP (1-27) were equipotent and VIP (1-26) and VIP (1-25) were 10- and 300-fold less potent, respectively; secretin (1-27) and secretin (1-26) were of equally low affinity and 10-fold more potent than secretin (1-24). Thus, the secretin and the VIP1 receptors had different selectivity profiles for the recognition of C-terminally truncated secretin and VIP derivatives. The chimeric receptors consisting in the N-terminal part of the secretin receptor on the core of the VIP1 receptor (N-Sn/VIP1.r) and in the N-terminal part of the VIP1 receptor on the core of the secretin receptor (N-VIP1/Sn.r) exhibited the selectivity pattern of the secretin and VIP1 receptors, respectively. The results suggest that the C-terminal end of secretin and VIP interacts with the N-terminal domain of the secretin and VIP receptors.
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: J P
authors.initials: JP
authors.lastname: Vilardaga
authors.forename: P
authors.initials: P
authors.lastname: De Neef
authors.forename: M
authors.initials: M
authors.lastname: Waelbroeck
authors.forename: A
authors.initials: A
authors.lastname: Vandermeers
authors.forename: P
authors.initials: P
authors.lastname: Robberecht
mesh_terms: D000262:Adenylyl Cyclases / Q000235:genetics / Q000378:metabolism; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000235:genetics; D007457:Iodine Radioisotopes; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000378:metabolism*; D011869:Radioligand Assay; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D018005:Receptors, Vasoactive Intestinal Peptide / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012633:Secretin / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000032:analysis / Q000737:chemistry / Q000378:metabolism*
chemical_list: D007457:Iodine Radioisotopes; D008565:Membrane Proteins; D010446:Peptide Fragments; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; C029937:secretin receptor; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases