Effect of introduction of an arginine16 in VIP, PACAP and secretin on ligand affinity for the receptors.
Rabbit secretin, which differs from all other mammalian secretins in having a Leu residue in position 6 (instead of Phe) and a basic residue (Arg) in position 16, had a lower affinity than porcine secretion on recombinant rat secretin receptors but had a greater affinity than porcine secretin on recombinant rat VIP1 and PACAP I receptors. Synthetic [L6] porcine secretin had a reduced potency on secretin and VIP1 receptors whereas [R16] porcine secretin had a similar binding profile as rabbit secretin. Thus, an arginine residue in position 16 reduced 3-fold the affinity of secretin for secretin receptors but increased 30-fold its affinity for the VIP1 and PACAP I receptors. The introduction of an arginine residue in position 16, instead of glutamine, in VIP and PACAP had a similar effect: [R16] VIP and [R16] PACAP had 3- to 10-fold higher affinities than VIP and PACAP for VIP1 and PACAP I receptors, and 3-fold lower affinities for the secretin receptors. The three [R16] peptides also had a reduced potency on the chimeric receptor consisting of the N-terminal part of the secretin receptor grafted on the VIP1 receptor, and an enhanced potency on the chimeric receptor consisting of the N-terminal part of VIP1 receptor grafted on the secretin receptor, indicating that position 16 of each ligand interacted with the N-terminal extracellular domain of the receptors.
Gourlet
P
P
Department of Biochemistry and Nutrition, Faculty of Medicine, Université Libre de Bruxelles, Belgium.
Vandermeers
A
A
Vandermeers-Piret
M C
MC
De Neef
P
P
Waelbroeck
M
M
Robberecht
P
P
D000818:Animals; D001120:Arginine / Q000502:physiology*; D016466:CHO Cells; D006224:Cricetinae; D008024:Ligands; D009479:Neuropeptides / Q000378:metabolism*; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011817:Rabbits; D051381:Rats; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone / Q000235:genetics / Q000378:metabolism; D018000:Receptors, Peptide / Q000378:metabolism*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone / Q000235:genetics / Q000378:metabolism; D018005:Receptors, Vasoactive Intestinal Peptide / Q000235:genetics / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012633:Secretin / Q000378:metabolism; D013552:Swine; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
C495403:Adcyap1 protein, rat; D008024:Ligands; D009479:Neuropeptides; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D043562:Receptors, G-Protein-Coupled; D011964:Receptors, Gastrointestinal Hormone; D018000:Receptors, Peptide; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011993:Recombinant Fusion Proteins; C029937:secretin receptor; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D001120:Arginine