PYY3-36 inhibits the action potential firing activity of POMC neurons of arcuate nucleus through postsynaptic Y2 receptors.
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.
Ghamari-Langroudi
Masoud
M
Vollum Institute and Center for the Study of Weight Regulation and Associated Disorders, Oregon Health and Science University, 3181 SW Sam Jackson Park Road, Portland, Oregon 97239, USA.
Colmers
William F
WF
Cone
Roger D
RD
D000200:Action Potentials / Q000187:drug effects*; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology* / Q000187:drug effects / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D049452:Green Fluorescent Proteins / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D018408:Patch-Clamp Techniques; D019894:Peptide YY / Q000494:pharmacology*; D011333:Pro-Opiomelanocortin / Q000378:metabolism*; D017476:Receptors, Neuropeptide Y / Q000502:physiology*; D013997:Time Factors
D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; D049452:Green Fluorescent Proteins; D011333:Pro-Opiomelanocortin