Structural requirements for the binding of the pituitary adenylate-cyclase-activating peptide to receptors and adenylate-cyclase activation in pancreatic and neuronal membranes

Eur J Biochem. 1991 Jan 30;195(2):535-41. doi: 10.1111/j.1432-1033.1991.tb15734.x.


PACAP (pituitary adenylate-cyclase-activating peptide)-binding receptors were investigated in membranes from the rat pancreatic acinar cell line, AR 4-2J, the rat hippocampus and the human neuroblastoma cell line NB-OK, by 125I-PACAP(1-27) (amino acid residues 1-27 of N-terminal amidated PACAP) binding and adenylate cyclase activation. The relative binding of 125I-PACAP(1-27) to the receptor, and ability to activate adenylate cyclase were PACAP greater than or equal to PACAP(1-27) greater than PACAP(2-38) greater than PACAP(1-9)-VIP(10-28)(PACAP-VIP) greater than PACAP(2-27) greater than [Ser9,Tyr13]VIP greater than [Tyr13]VIP greater than or equal to [Ser9]VIP greater than or equal to VIP(1-23)-PACAP(24-27)(VIP-PACAP) greater than VIP (vasoactive intestinal peptide). The N-terminal moiety of PACAP(1-27) was more important than the three amino acids at the C-terminus for 125I-PACAP(1-27)-binding site recognition. For rat pancreatic 125I-VIP-binding sites tested with 125I-VIP, the order of binding affinity was PACAP = PACAP(1-27) greater than or equal to VIP = [Ser9]VIP = [Tyr13]VIP = [Ser9,Try13]VIP greater than or equal to PACAP-VIP greater than or equal to VIP-PACAP greater than PACAP(2-38) = PACAP(2-27). Pancreatic 125I-VIP-binding sites, when compared to 125I-PACAP(1-27)-binding sites, showed little specificity and only weak coupling, so that PACAP and VIP-PACAP acted only as partial VIP agonists on adenylate cyclase.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • Cell Membrane / enzymology
  • Chimera
  • Enzyme Activation
  • Hippocampus / enzymology*
  • Humans
  • Molecular Sequence Data
  • Neuroblastoma / enzymology*
  • Neurons / enzymology
  • Neuropeptides / chemistry*
  • Pancreatic Neoplasms / drug therapy
  • Pancreatic Neoplasms / enzymology*
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Rats
  • Tumor Cells, Cultured
  • Vasoactive Intestinal Peptide / metabolism


  • ADCYAP1 protein, human
  • Adcyap1 protein, rat
  • Neuropeptides
  • Pituitary Adenylate Cyclase-Activating Polypeptide
  • Vasoactive Intestinal Peptide
  • Adenylyl Cyclases