title: Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus.
abstract: The recently discovered hormone ghrelin, which is secreted from the stomach during fasting and hypoglycemia opposes the homeostatic functions of leptin by increasing food intake and decreasing energy expenditure. The hypothalamic arcuate nucleus (Arc) mediates the effects of leptin and contains a high density of ghrelin receptors. The leptin- and ghrelin-responsive network involves the hypothalamic neuropeptide Y/alpha-melanocyte stimulating hormone (NPY/alpha-MSH) system. In the rat, neurons expressing the orexigenic peptide NPY are mainly located in the ventromedial Arc (ArcM), while pro-opiomelanocortin (POMC) neurons, synthesizing the anorectic peptide alpha-MSH, predominate in the ventrolateral Arc (ArcL). In extracellular single unit recordings from in vitro slice preparations of the Arc, superfusion of ghrelin (10(-8) M) exerted predominantly excitatory effects on ArcM neurons (73%, n=93), while a high number ArcL neurons were inhibited in response to ghrelin (42%, n=43). The excitatory effect of ghrelin on neuronal activity was postsynaptic since it was unaffected by synaptic blockade (low Ca(2+)/high Mg(2+) solution). In contrast, the inhibitory response in the ArcL was abolished by the blockade of synaptic interactions indicating a presynaptic mechanism. These results indicate that circulating ghrelin may oppose the actions of leptin by directly activating NPY-neurons of the ArcM and by indirectly inhibiting POMC neurons of the ArcL.
authors.affiliation: Institute of Veterinary Physiology, University of Zurich, Winterthurerstrasse 260, 8057, Zurich, Switzerland.
authors.forename: Thomas
authors.initials: T
authors.lastname: Riediger
authors.forename: Martin
authors.initials: M
authors.lastname: Traebert
authors.forename: Herbert A
authors.initials: HA
authors.lastname: Schmid
authors.forename: Caroline
authors.initials: C
authors.lastname: Scheel
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Lutz
authors.forename: Erwin
authors.initials: E
authors.lastname: Scharrer
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001111:Arcuate Nucleus of Hypothalamus / Q000166:cytology / Q000187:drug effects*; D002118:Calcium / Q000494:pharmacology; D054439:Ghrelin; D066298:In Vitro Techniques; D008274:Magnesium / Q000494:pharmacology; D008297:Male; D009433:Neural Inhibition / Q000187:drug effects; D009474:Neurons / Q000187:drug effects* / Q000502:physiology; D036361:Peptide Hormones / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D011930:Reaction Time
chemical_list: D054439:Ghrelin; D036361:Peptide Hormones; D008274:Magnesium; D002118:Calcium