Serotonin 2C receptor activates a distinct population of arcuate pro-opiomelanocortin neurons via TRPC channels

Neuron. 2011 Aug 11;71(3):488-97. doi: 10.1016/j.neuron.2011.06.012.

Abstract

Serotonin 2C receptors (5-HT(2C)Rs) expressed by pro-opiomelanocortin (POMC) neurons of hypothalamic arcuate nucleus regulate food intake, energy homeostasis and glucose metabolism. However, the cellular mechanisms underlying the effects of 5-HT to regulate POMC neuronal activity via 5-HT(2C)Rs have not yet been identified. In the present study, we found the putative transient receptor potential C (TRPC) channels mediate the activation of a subpopulation of POMC neurons by mCPP (a 5-HT(2C)R agonist). Interestingly, mCPP-activated POMC neurons were found to be a distinct population from those activated by leptin. Together, our data suggest that 5-HT(2C)R and leptin receptors are expressed by distinct subpopulations of arcuate POMC neurons and that both 5-HT and leptin exert their actions in POMC neurons via TRPC channels.

Publication types

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

MeSH terms

  • Animals
  • Arcuate Nucleus of Hypothalamus / drug effects
  • Arcuate Nucleus of Hypothalamus / physiology*
  • G Protein-Coupled Inwardly-Rectifying Potassium Channels / physiology
  • Leptin / pharmacology
  • Leptin / physiology
  • Male
  • Membrane Potentials / physiology
  • Mice
  • Mice, Transgenic
  • Neurons / physiology*
  • Patch-Clamp Techniques / methods
  • Piperazines / pharmacology
  • Pro-Opiomelanocortin / genetics
  • Pro-Opiomelanocortin / physiology*
  • Receptor, Serotonin, 5-HT2C / physiology*
  • Serotonin / pharmacology
  • Serotonin / physiology
  • Serotonin 5-HT2 Receptor Agonists / pharmacology
  • TRPC Cation Channels / antagonists & inhibitors
  • TRPC Cation Channels / physiology*

Substances

  • G Protein-Coupled Inwardly-Rectifying Potassium Channels
  • Leptin
  • Piperazines
  • Receptor, Serotonin, 5-HT2C
  • Serotonin 5-HT2 Receptor Agonists
  • TRPC Cation Channels
  • Serotonin
  • Pro-Opiomelanocortin
  • 1-(3-chlorophenyl)piperazine