A comparison of actions of neuropeptide Y (NPY) agonists and antagonists at NPY Y1 and Y2 receptors in anaesthetized rats.

Abstract

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.