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

Publisher Website
Google Scholar
Abstract
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 ≥ PACAP(1–27) > PACAP(2–38) > PACAP(1–9)-VIP(10–28)(PACAP-VIP) > PACAP(2–27) > [Ser9, Tyr13]VIP > [Tyr13]VIP ≥ [Ser9]VIP ≥ VIP(1–23)-PACAP(24–27)(VIP-PACAP) > 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) ≥ VIP = [Ser9]VIP = [Tyr13]VIP = [Ser9, Tyr13]VIP ≥ PACAP-VIP ≥ VIP-PACAP > 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.

This publication has 24 references indexed in Scilit: