Orexigen-sensitive NPY/AgRP pacemaker neurons in the hypothalamic arcuate nucleus.
The hypothalamic arcuate nucleus (ARC) integrates and responds to satiety and hunger signals and forms the origins of the central neural response to perturbations in energy balance. Here we show that rat ARC neurons containing neuropeptide Y (NPY) and agouti-related protein (AgRP), which are conditional pacemakers, are activated by orexigens and inhibited by the anorexigen leptin. We propose a neuron-specific signaling mechanism through which central and peripheral signals engage the central neural anabolic drive.
van den Top
Marco
M
Department of Biological Sciences, Gibbet Hill Campus, University of Warwick, Coventry CV4 7AL, UK.
Lee
Kevin
K
Whyment
Andrew D
AD
Blanks
Andrew M
AM
Spanswick
David
D
D015761:4-Aminopyridine / Q000494:pharmacology; D054369:Agouti-Related Protein; D000779:Anesthetics, Local / Q000494:pharmacology; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology*; D002352:Carrier Proteins / Q000494:pharmacology; D004347:Drug Interactions; D054439:Ghrelin; D066298:In Vitro Techniques; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin / Q000494:pharmacology; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009478:Neuropeptide Y / Q000378:metabolism*; D009479:Neuropeptides / Q000494:pharmacology; D009532:Nickel / Q000494:pharmacology; D064446:Orexin Receptors; D000068797:Orexins; D018408:Patch-Clamp Techniques; D036361:Peptide Hormones / Q000494:pharmacology; D026902:Potassium Channel Blockers / Q000494:pharmacology; D011506:Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D051381:Rats; D017208:Rats, Wistar; D011956:Receptors, Cell Surface / Q000235:genetics / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D054411:Receptors, Leptin; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D013779:Tetrodotoxin / Q000494:pharmacology
C515197:AGRP protein, rat; D054369:Agouti-Related Protein; D000779:Anesthetics, Local; D002352:Carrier Proteins; D054439:Ghrelin; D036341:Intercellular Signaling Peptides and Proteins; D047908:Intracellular Signaling Peptides and Proteins; D020738:Leptin; D009478:Neuropeptide Y; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D036361:Peptide Hormones; D026902:Potassium Channel Blockers; D011506:Proteins; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D054411:Receptors, Leptin; D018013:Receptors, Neuropeptide; D013779:Tetrodotoxin; D009532:Nickel; D015761:4-Aminopyridine