title: Neuropeptide Y and neuropeptide Y18-36. Structural and biological characterization.
abstract: Neuropeptide Y (NPY), a 36-residue peptide amide, has been shown by numerous studies to be a potent vasoconstrictor. In order to gain an appreciation of the structural requirements for this action, we have previously synthesized a number of fragments of NPY. It had been shown that sequential deletions from the N-terminus resulted in peptides with decreasing hypertensive activity. In the present study we present data supporting the unexpected finding of two fragments, NPY17-36 and NPT18-36 with substantial hypotensive action in vivo. This action was dose dependent (data not shown) and was also observed to a lesser extent with NPY19-36 but not NPY16-36 or NPY20-36. It was, however, slower in onset and of longer duration than the hypertensive action of NPY. These differing kinetics of action may suggest that NPY and NPY18-36 act through different mechanisms. Structural studies using circular dichroism were performed. While NPY was found to assume an ordered helical structure in both aqueous buffer and trifluoroethanol (TFE), 30% TFE in aqueous buffer was required to induce substantial helicity for NPY18-36. This structural investigation suggests that both NPY and NPY18-36 assume an ordered conformation upon reaching the lipid rich receptor environment.
authors.affiliation: Clayton Foundation Laboratories for Peptide Biology, Salk Institute, San Diego, CA.
authors.forename: J
authors.initials: J
authors.lastname: Boublik
authors.forename: N
authors.initials: N
authors.lastname: Scott
authors.forename: J
authors.initials: J
authors.lastname: Taulane
authors.forename: M
authors.initials: M
authors.lastname: Goodman
authors.forename: M
authors.initials: M
authors.lastname: Brown
authors.forename: J
authors.initials: J
authors.lastname: Rivier
mesh_terms: D000818:Animals; D000959:Antihypertensive Agents; D001794:Blood Pressure / Q000187:drug effects; D002942:Circular Dichroism; D006973:Hypertension / Q000139:chemically induced; D008297:Male; D009478:Neuropeptide Y / Q000494:pharmacology*; D010446:Peptide Fragments / Q000494:pharmacology*; D011487:Protein Conformation; D051381:Rats; D011919:Rats, Inbred Strains; D013329:Structure-Activity Relationship
chemical_list: D000959:Antihypertensive Agents; D009478:Neuropeptide Y; D010446:Peptide Fragments; C059889:neuropeptide Y (18-36)