title: Involvement of PKA and ERK pathways in ghrelin-induced long-lasting potentiation of excitatory synaptic transmission in the CA1 area of rat hippocampus.
abstract: Acute effects of ghrelin on excitatory synaptic transmission were evaluated on hippocampal CA1 synapses. Ghrelin triggered an enduring enhancement of synaptic transmission independently of NMDA receptor activation and probably via postsynaptic modifications. This ghrelin-mediated potentiation resulted from the activation of GHS-R1a receptors as it was mimicked by the selective agonist JMV1843 and blocked by the selective antagonist JMV2959. This potentiation also required the activation of PKA and ERK pathways to occur as it was inhibited by KT5720 and U0126, respectively. Moreover it most probably involved Ca(2+) influxes as both ghrelin and JMV1843 elicited intracellular Ca(2+) increases, which were dependent on the presence of extracellular Ca(2+) and mediated by L-type Ca(2+) channels opening. In addition, ghrelin potentiated AMPA receptor-mediated [Ca(2+) ]i increases while decreasing NMDA receptor-mediated ones. Thus the potentiation of synaptic transmission by GHS-R1a at hippocampal CA1 excitatory synapses probably results from postsynaptic mechanisms involving PKA and ERK activation, which are producing long-lasting enhancement of AMPA receptor-mediated responses.
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Mélanie
authors.initials: M
authors.lastname: Cavalier
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Nadine
authors.initials: N
authors.lastname: Crouzin
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Azza
authors.initials: A
authors.lastname: Ben Sedrine
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Marie Celeste
authors.initials: MC
authors.lastname: de Jesus Ferreira
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Janique
authors.initials: J
authors.lastname: Guiramand
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Catherine
authors.initials: C
authors.lastname: Cohen-Solal
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Jean-Alain
authors.initials: JA
authors.lastname: Fehrentz
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Jean
authors.initials: J
authors.lastname: Martinez
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Barbanel
authors.affiliation: Institut des Biomolécules Max Mousseron, UMR 5247 CNRS-University of Montpellier, Place E Bataillon, 34095, Montpellier Cedex 5, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Vignes
mesh_terms: D000818:Animals; D056547:CA1 Region, Hippocampal / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism; D020746:Calcium Channels, L-Type / Q000378:metabolism; D002478:Cells, Cultured; D002491:Central Nervous System Agents / Q000008:administration & dosage; D017868:Cyclic AMP-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D054439:Ghrelin / Q000008:administration & dosage / Q000378:metabolism*; D017774:Long-Term Potentiation / Q000187:drug effects / Q000502:physiology*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D017207:Rats, Sprague-Dawley; D018091:Receptors, AMPA / Q000378:metabolism; D054440:Receptors, Ghrelin / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D046509:Tissue Culture Techniques
chemical_list: D020746:Calcium Channels, L-Type; D002491:Central Nervous System Agents; D054439:Ghrelin; D018091:Receptors, AMPA; D054440:Receptors, Ghrelin; D016194:Receptors, N-Methyl-D-Aspartate; D017868:Cyclic AMP-Dependent Protein Kinases; D002118:Calcium
keywords: AMPA; GHS-R1a; Hippocampus; NMDA; intracellular calcium; plasticity