A comparison of actions of neuropeptide Y (NPY) agonists and antagonists at NPY Y1 and Y2 receptors in anaesthetized rats.
The pancreatic polypeptide family includes three members, neuropeptide Y (NPY), peptide YY (PYY) and pancreatic polypeptide (PP), with sequence homology between members and species varying from approximately 50 to 80%. Some of these peptides were compared in the mammalian cardiovascular system for activity mediated by actions on pre- (Y2) and post-junctional (Y1) NPY receptors. NPY and PYY, with sequence homology of 67% have similar actions on Y1 and Y2 receptors. Rat pancreatic polypeptide (rPP) with sequence homology of approximately 50% is inactive at both. This study reports that the chimeric peptide, hPP1-11/NPY12-36 and the truncated peptide NPY2-36 show similar activity to NPY mediated through both receptor types in vivo, while salmon PYY (sPYY), with 81% homology to NPY, has improved potency at both receptor subtypes. NPY3-36 has equal activity with NPY on actions mediated through Y2 receptors, but significantly reduced activity mediated through Y1 receptors. Two NPY antagonists were also examined: PYX2 was inactive in vivo and 1229U91 showed potent, long-lasting activity on Y1 receptor-mediated effects.
Smith-White
M
M
Prince of Wales Medical Research Institute, Sydney, NSW, Australia.
Moriarty
M J
MJ
Potter
E K
EK
D000758:Anesthesia; D000818:Animals; D004305:Dose-Response Relationship, Drug; D005260:Female; D006321:Heart / Q000294:innervation; D006801:Humans; D009478:Neuropeptide Y / Q000031:analogs & derivatives / Q000494:pharmacology*; D010191:Pancreatic Polypeptide / Q000494:pharmacology; D010446:Peptide Fragments / Q000494:pharmacology*; D010456:Peptides, Cyclic / Q000494:pharmacology*; D011498:Protein Precursors / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000819:agonists / Q000037:antagonists & inhibitors / Q000502:physiology*; D011993:Recombinant Fusion Proteins / Q000494:pharmacology; D012474:Salmon; D013569:Synapses / Q000737:chemistry / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
C097287:1229U91; D009478:Neuropeptide Y; D010446:Peptide Fragments; D010456:Peptides, Cyclic; D011498:Protein Precursors; D017476:Receptors, Neuropeptide Y; D011993:Recombinant Fusion Proteins; C083514:neuropeptide Y (2-36); C113547:neuropeptide Y (3-36); C097212:neuropeptide Y-Y1 receptor; C095889:neuropeptide Y2 receptor; C081158:proneuropeptide Y; C079216:PYX 2; D010191:Pancreatic Polypeptide