Molecular recognition of vasoactive peptides : basis for Physiological action

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The structure of pituitary adenylate activating polypeptide (PACAP) and (PACAP) related peptide (PRP) were investigated by CD and NMR spectroscopy, distance geometry, molecular dynamics and energy minimization calculations. PACAP38 and 27 had an initial disordered N-terminal structure, followed by a helical structures. PRP had a helical structure from 3-20th. Based on these results, several PACAP related peptides were synthesized by a solid phase peptide synthesizer. PACAP was a potent vosodilator. Vascular effects of PACAP was independent of the endothelium and was not blocked by NO synthase inhibitors.PACAP37,36,35,34, and 33 had similar peak vascular effects to PACAP38 but the duration of action was dependent on the length of the peptide. PACAP had an opposite effect to VIP on the guinea pig gallbladder. The C-terminus of PACAP and VIP,where two peptides show the largest difference in sequence, was not important for the recognition of them but the N-terminal flexible portion was responsible for their opposite actions on the gallbladder. Tissue distribution of PACAP38, PACAP27, and PRP in guinea pigs was investigated by radioimmunoassay. Significant amounts of PACAP/PRP were present not only in the central nervous system but also in the gastrointestinal tract, where they were present in the enteric neurons. Several fragments of endothelin and secretin receptors were chemically synthesized and their specific antibodies were raised. On immunoblotts of pancreatic membranes subjected to SDS-polyacrylamide gel electrophoresis, antisera against secretin receptor fragments showed positive bands around 50kDa. Rat pancreatic ducts were strongly stained and acini with less degree by these antisera.