The C-terminal part of VIP is important for receptor binding and activation, as evidenced by chimeric constructs of VIP/secretin.
The structural requirements of vasoactive intestinal polypeptide (VIP) for receptor binding and cAMP production were studied in a cell line stable transfected with the cDNA for rat VIP receptor 1 (rVIPR 1). Using a number of chimeric constructs of VIP and the homologue peptide secretin, it was found that the N-terminal half of VIP (1-11) can be exchanged with the corresponding sequences in secretin with only modest influence on binding and activation, whereas the opposite chimeras with N-terminal VIP and C-terminal secretin were unable to bind to the VIP receptor. The data suggest that the C-terminal region of VIP is important for receptor binding and activation.
Wulff
B
B
Department of Molecular Pharmacology, Novo-Nordisk Park, Måløv, Denmark.
Møller Knudsen
S
S
Adelhorst
K
K
Fahrenkrug
J
J
D015056:1-Methyl-3-isobutylxanthine / Q000494:pharmacology; D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D016466:CHO Cells; D006224:Cricetinae; D000242:Cyclic AMP / Q000378:metabolism; D004789:Enzyme Activation; D007700:Kinetics; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051381:Rats; D018005:Receptors, Vasoactive Intestinal Peptide / Q000096:biosynthesis / Q000502:physiology*; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011993:Recombinant Fusion Proteins / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000096:biosynthesis; D012633:Secretin / Q000737:chemistry; D014162:Transfection; D014660:Vasoactive Intestinal Peptide / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*
D010446:Peptide Fragments; D018005:Receptors, Vasoactive Intestinal Peptide; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D011993:Recombinant Fusion Proteins; D011994:Recombinant Proteins; D012633:Secretin; D014660:Vasoactive Intestinal Peptide; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D015056:1-Methyl-3-isobutylxanthine