Nesfatin-1 inhibits NPY neurons in the arcuate nucleus.
Although the novel satiety factor nesfatin-1 has been shown to influence feeding behavior through effects on melanocortin signaling, the specific hypothalamic neuronal substrates through which such effects are mediated have yet to be elucidated. To identify neuronal cell types potentially important in mediating nesfatin-1's effects, whole cell current clamp recordings were made from hypothalamic arcuate nucleus neurons and the effects of bath applied nesfatin-1 on membrane excitability determined. Neurons then underwent phenotypic identification post hoc using single cell RT-PCR. Nesfatin-1 (10 nM) had effects on the majority of arcuate nucleus neurons tested, with most responsive cells hyperpolarizing following exposure. Furthermore, 9 of 11 identified NPY neurons hyperpolarized in response to nesfatin-1 exposure. Pharmacological experiments revealed that glibenclamide (500 nM), an ATP-sensitive potassium conductance antagonist, prevented nesfatin-1-induced hyperpolarization. Therefore, nesfatin-1-induced inhibition of feeding may be mediated through the inhibition of orexigenic NPY neurons.
Price
Christopher J
CJ
Department of Physiology, Queen's University, Kingston, ON, Canada, K7L 3N6.
Samson
Willis K
WK
Ferguson
Alastair V
AV
D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D004594:Electrophysiology; D005905:Glyburide / Q000494:pharmacology; D007031:Hypothalamus / Q000166:cytology / Q000187:drug effects; D066298:In Vitro Techniques; D054086:KATP Channels / Q000187:drug effects; D008297:Male; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000502:physiology*; D009478:Neuropeptide Y / Q000502:physiology*; D000080866:Nucleobindins; D026902:Potassium Channel Blockers / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013779:Tetrodotoxin / Q000494:pharmacology
D000779:Anesthetics, Local; D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D054086:KATP Channels; D009419:Nerve Tissue Proteins; D009478:Neuropeptide Y; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D026902:Potassium Channel Blockers; D013779:Tetrodotoxin; D005905:Glyburide