The identification of neuropeptide Y receptor subtype involved in phenylpropanolamine-induced increase in oxidative stress and appetite suppression

Neuromolecular Med. 2013 Mar;15(1):159-68. doi: 10.1007/s12017-012-8206-x. Epub 2012 Nov 20.


Hypothalamic neuropeptide Y (NPY) and superoxide dismutase (SOD) have been reported to participate in the regulation of appetite-suppressing effect of phenylpropanolamine (PPA), a sympathomimetic agent. This study explored whether Y1 receptor (Y1R) and/or Y5 receptor (Y5R) was involved in this regulation. Wistar rats were treated with PPA for 24 h. Changes in food intake and hypothalamic NPY, Y1R, Y5R, and SOD contents were assessed and compared. Results showed that food intake and NPY contents were decreased following PPA treatment, while Y1R and SOD contents were increased and Y5R contents remained unchanged. Moreover, although Y1R or Y5R knockdown by themselves could modify the food intake, Y1R but not Y5R knockdown could modify PPA-induced anorexia as well as NPY and SOD contents. In addition, selective inhibition of Y1R but not Y5R could modulate PPA-induced anorexia. It is suggested that Y1R but not Y5R participates in the anorectic response of PPA via the modulation of NPY and SOD. Results provide molecular mechanism of NPY-mediated PPA anorexia and may aid the understanding of the toxicology of PPA.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anorexia / chemically induced*
  • Anorexia / physiopathology
  • Appetite / drug effects
  • Appetite Depressants / toxicity*
  • Gene Knockdown Techniques
  • Hypothalamus / chemistry
  • Hypothalamus / drug effects
  • Hypothalamus / physiopathology
  • Injections, Intraventricular
  • Male
  • Neuropeptide Y / physiology*
  • Oligonucleotides, Antisense / pharmacology
  • Oxidative Stress / drug effects*
  • Phenylpropanolamine / toxicity*
  • Rats
  • Rats, Wistar
  • Receptors, G-Protein-Coupled / antagonists & inhibitors
  • Receptors, G-Protein-Coupled / genetics
  • Receptors, G-Protein-Coupled / physiology*
  • Receptors, Neuropeptide / antagonists & inhibitors
  • Receptors, Neuropeptide / genetics
  • Receptors, Neuropeptide / physiology*
  • Receptors, Neuropeptide Y / antagonists & inhibitors
  • Receptors, Neuropeptide Y / genetics
  • Receptors, Neuropeptide Y / physiology
  • Superoxide Dismutase / physiology*
  • Sympathomimetics / toxicity*


  • Appetite Depressants
  • Neuropeptide Y
  • Npy1r protein, rat
  • Oligonucleotides, Antisense
  • Receptors, G-Protein-Coupled
  • Receptors, Neuropeptide
  • Receptors, Neuropeptide Y
  • Sympathomimetics
  • neuropeptide Y5 receptor
  • Phenylpropanolamine
  • Superoxide Dismutase
  • superoxide dismutase 2