Open AccessStructural requirements for the binding of the pituitary adenylate‐cyclase‐activating peptide to receptors and adenylate‐cyclase activation in pancreatic and neuronal membranes
Author(s) -
GOURLET Philippe,
WOUSSENCOLLE MarieClaire,
ROBBERECHT Patrick,
NEEF Philippe,
CAUVIN Annick,
VANDERMEERSPIRET MarieClaire,
VANDERMEERS André,
CHRISTOPHE Jean
Publication year - 1991
Publication title -
european journal of biochemistry
Language(s) - English
Resource type - Journals
eISSN - 1432-1033
pISSN - 0014-2956
DOI - 10.1111/j.1432-1033.1991.tb15734.x
Subject(s) - vasoactive intestinal peptide , pituitary adenylate cyclase activating peptide , cyclase , adenylate kinase , receptor , endocrinology , neuropeptide , medicine , chemistry , biology , biochemistry
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 125 I‐PACAP(1–27) (amino acid residues 1–27 of N‐terminal amidated PACAP) binding and adenylate cyclase activation. The relative binding of 125 I‐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 125 I‐PACAP(1–27)‐binding site recognition. For rat pancreatic 125 I‐VIP‐binding sites tested with 125 I‐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 125 I‐VIP‐binding sites, when compared to 125 I‐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.