Peptide YY derivatives as selective neuropeptide Y/peptide YY Y1 and Y2 agonists devoided of activity for the Y3 receptor sub-type

Brain Res Mol Brain Res. 1994 Oct;26(1-2):320-4. doi: 10.1016/0169-328x(94)90105-8.

Abstract

Peptide YY derivatives were evaluated for their respective ability to bind and activate the NPY/PYY receptor sub-types (Y1, Y2 and Y3) present in various preparations. The analogue [Leu31,Pro34]PYY demonstrated high (nM) affinity in rat frontoparietal cortical membrane preparations (Y1-enriched tissue) and the rabbit saphenous vein (Y1 in vitro bioassay) but only low affinity in a Y2-enriched preparation (rat hippocampus). In contrast, PYY C-terminal fragments such as PYY3-36 and PYY13-36 were more potent in Y2 than Y1 assays. Interestingly, and in contrast to [Leu31,Pro34]NPY and NPY13-36, the PYY derivatives [Leu31,Pro34]PYY and PYY3-36 were inactive in a purported Y3 bioassay (rat colon). These results suggest that [Leu31,Pro34]PYY and PYY3-36 respectively represent the first selective and potent Y1 and Y2 agonists, devoided of significant affinity/activity for the Y3 receptor class.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Binding, Competitive
  • Biological Assay
  • Cell Membrane / metabolism
  • Colon / drug effects
  • Colon / physiology
  • Gastrointestinal Hormones / pharmacology
  • Hippocampus / metabolism*
  • In Vitro Techniques
  • Kinetics
  • Male
  • Muscle Contraction / drug effects
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / physiology
  • Muscle, Smooth, Vascular / drug effects
  • Muscle, Smooth, Vascular / physiology
  • Neuropeptide Y / agonists*
  • Peptide YY
  • Peptides / agonists
  • Peptides / pharmacology*
  • Rabbits
  • Rats
  • Receptors, Neuropeptide Y / metabolism*
  • Saphenous Vein / drug effects
  • Saphenous Vein / physiology
  • Structure-Activity Relationship
  • Vas Deferens / drug effects
  • Vas Deferens / physiology

Substances

  • Gastrointestinal Hormones
  • Neuropeptide Y
  • Peptides
  • Receptors, Neuropeptide Y
  • Peptide YY