Investigation of the interaction of VIP binding sites with VIP and PACAP in human brain.
We have compared the binding of [125I]vasoactive intestinal polypeptide (VIP) to human brain membranes with that of [125I]PACAP27. [125I]VIP was displaced by PACAP27, VIP and two synthetic peptides, peptide-1 (N-terminal PACAP27/C-terminal VIP) and peptide-2 (N-terminal VIP/C-terminal PACAP27), but the IC50 of PACAP27 and peptide-1 were 10-20 times lower than those of VIP and peptide-2. [125I]PACAP27 was readily displaced by PACAP27 and peptide-1, with an IC50 of less than 1 nM, but poorly by VIP and peptide-2. Chemical cross-linking revealed that both labels were bound to polypeptides of Mr 66,000 and Mr 50,000. The results indicate that in human brain membranes both binding sites have a higher affinity to the N-terminal sequence of PACAP27, and VIP binding sites prefer PACAP27 to VIP itself.
Suda
K
K
Department of Medicine, Royal Postgraduate Medical School, Hammersmith Hospital, London, UK.
Smith
D M
DM
Ghatei
M A
MA
Bloom
S R
SR
D000262:Adenylyl Cyclases / Q000378:metabolism; D000595:Amino Acid Sequence; D006801:Humans; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000378:metabolism*; D010446:Peptide Fragments / Q000378:metabolism; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011964:Receptors, Gastrointestinal Hormone / Q000378:metabolism*; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide
C495401:ADCYAP1 protein, human; D009479:Neuropeptides; D010446:Peptide Fragments; D051219:Pituitary Adenylate Cyclase-Activating Polypeptide; D011956:Receptors, Cell Surface; D011964:Receptors, Gastrointestinal Hormone; D051236:Receptors, Pituitary Adenylate Cyclase-Activating Polypeptide; D011979:Receptors, Pituitary Hormone; D018005:Receptors, Vasoactive Intestinal Peptide; D000262:Adenylyl Cyclases