Characterization of Y3 receptor-mediated synaptic inhibition by chimeric neuropeptide Y-peptide YY peptides in the rat brainstem

Forskningsoutput: TidskriftsbidragArtikel i vetenskaplig tidskrift

Abstract

1. Neuropeptide Y (NPY) and peptide YY (PYY) act at receptors referred to as Y1 and Y2, while the Y3 receptor is specific to NPY and does not recognize PYY. The effects of NPY, its related peptides and a series of newly constructed chimeric NPY-PYY peptides were examined on excitatory and inhibitory postsynaptic currents (e.p.s.cs and i.p.s.cs, respectively) in rat dorsomedial nucleus tractus solitarius (NTS) neurones recorded in coronal brainstem slices. Monosynaptic activity was evoked by electrical stimulation in the region of the tractus solitarius. 2. NPY (5-500 nM) inhibited e.p.s.cs and i.p.s.cs in a concentration-dependent manner. In contrast, PYY (500 nM) failed to affect either e.p.s.cs or i.p.s.cs. The N- and C-terminal parts of a series of chimeric NPY-PYY peptides were joined at positions where NPY and PYY sequences differ. In binding experiments the chimeric peptides were all about equipotent with NPY and PYY in displacing [125I]-PYY from Y1 and Y2 binding sites on SK-N-MC cells and rat hippocampus respectively. 3. In the whole cell voltage clamp recordings of NTS neurones, NPY(1-23)-PYY(24-36) and NPY(1-14)-PYY(15-36) evoked a concentration-dependent inhibition of e.p.s.cs and i.p.s.cs, while NPY(1-7)-PYY(8-36) and NPY(1-3)-PYY(4-36) were inactive. The only differences in amino acid residues between NPY(1-14)-PYY(15-36) and NPY(1-7)-PYY(8-36) reside in positions 13 and 14. 4. Furthermore, [Pro34]NPY (500 nM) was equivalent in potency to NPY itself at inhibiting monosynaptic transmission in NTS, while [Leu31,Pro34]NPY and pancreatic polypeptide (both at 500 nM) failed to affect synaptic transmission. 5. The present study has shown that NPY acts at Y3 receptors to suppress both excitatory and inhibitory currents in the NTS. The different efficacy of the chimeric NPY-PYY peptides suggests that positions 13 and 14 are of great importance for Y3 receptor recognition. Finally, this receptor type readily recognizes [Pro34]NPY, but not [Leu31,Pro34]NPY.

Detaljer

Författare
  • S R Glaum
  • R J Miller
  • H Rhim
  • D Maclean
  • L M Georgic
  • R G MacKenzie
  • L Grundemar
Externa organisationer
  • Skåne University Hospital
Forskningsområden

Ämnesklassifikation (UKÄ) – OBLIGATORISK

  • Farmakologi och toxikologi

Nyckelord

Originalspråkengelska
Sidor (från-till)481-487
TidskriftBritish Journal of Pharmacology
Volym120
Utgivningsnummer3
StatusPublished - 1997 jan
PublikationskategoriForskning
Peer review utfördJa
Externt publiceradJa