PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors

Cell Metab. 2005 Sep;2(3):191-9. doi: 10.1016/j.cmet.2005.08.003.


Intracerebroventricular administration of gut peptide PYY3-36 stimulates food intake. In contrast, peripheral administration inhibits food intake, suggesting that the peptide has the opposite effect by virtue of accessing a unique subset of brain sites. A previous study suggested that peripheral PYY3-36 activates anorexigenic POMC neurons in the arcuate nucleus, and this was proposed to be the mechanism underlying the peptide's anorexigenic activity. Here, we demonstrate in an electrophysiological slice preparation that, in contrast to the original model, PYY3-36 potently and reversibly inhibits POMC neurons via postsynaptic Y2 receptors. These data show a complex role for Y2 receptors in regulation of the NPY/POMC circuitry, as they are present as inhibitory receptors on both the orexigenic NPY neurons as well as the anorexigenic POMC neurons. Secondly, these data argue against a direct role of POMC neurons in mediating the anorexigenic response to administration of peripheral PYY3-36.

Publication types

  • Comparative Study
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Action Potentials / drug effects*
  • Animals
  • Arcuate Nucleus of Hypothalamus / cytology*
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / physiology
  • Dose-Response Relationship, Drug
  • Green Fluorescent Proteins / metabolism
  • Mice
  • Mice, Transgenic
  • Neurons / drug effects*
  • Neurons / physiology
  • Patch-Clamp Techniques
  • Peptide YY / pharmacology*
  • Pro-Opiomelanocortin / metabolism*
  • Receptors, Neuropeptide Y / physiology*
  • Time Factors


  • Receptors, Neuropeptide Y
  • Peptide YY
  • Green Fluorescent Proteins
  • Pro-Opiomelanocortin