A novel neuropeptide Y analog, N-acetyl [Leu28,Leu31]neuropeptide Y-(24-36), with functional specificity for the presynaptic (Y2) receptor.
We have carried out functional and in vitro studies on a novel analog of neuropeptide Y which shows selectivity for the prejunctional or neuropeptide Y Y2 receptor. In anaesthetised rats N-acetyl [Leu28,Leu31]neuropeptide Y-(24-36) attenuates cardiac vagal action (a prejunctional or neuropeptide Y Y2 action) and has no significant pressor effects (postjunctional or neuropeptide Y Y1 action). In the human neuroblastoma cell line (SMS-KAN) which expresses and endogenous Y2-like neuropeptide Y receptor, N-acetyl [Leu28,Leu31]neuropeptide Y-(24-36) competes with peptide YY for binding sites with an IC50 of 0.5 +/- 0.1 nM. In contrast in a fibroblast Chinese hamster ovary cell line which expresses the cloned human neuropeptide Y Y1 receptor and is used to study changes in cytosolic calcium evoked by (a neuropeptide Y Y1 effect), N-acetyl [Leu28,Leu31]neuropeptide Y-(24-36) showed no activity even at high concentrations. The steric structure for this novel compound has been determined using proton nuclear magnetic resonance (NMR) spectroscopy and it is consistent with the C-terminal end of published structures of neuropeptide Y. We suggest acetylation and amino acid substitutions stabilise the molecule and allow it to bind only to the neuropeptide Y Y2 receptor.
Potter
E K
EK
Prince of Wales Medical Research Institute, Prince of Wales Hospital, Randwick, Sydney, NSW, Australia.
Barden
J A
JA
McCloskey
M J
MJ
Selbie
L A
LA
Tseng
A
A
Herzog
H
H
Shine
J
J
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D001667:Binding, Competitive; D001794:Blood Pressure / Q000187:drug effects; D016466:CHO Cells; D006224:Cricetinae; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D010446:Peptide Fragments / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology*; D019894:Peptide YY; D010455:Peptides / Q000378:metabolism; D017476:Receptors, Neuropeptide Y / Q000187:drug effects / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D009478:Neuropeptide Y; D010446:Peptide Fragments; D010455:Peptides; D017476:Receptors, Neuropeptide Y; C084653:neuropeptide Y (24-36), Ac-(Leu(28,31))-; D019894:Peptide YY