title: Vagal afferent fibres determine the oxytocin-induced modulation of gastric tone.
abstract: Oxytocin (OXT) inputs to the dorsal vagal complex (DVC; nucleus of the tractus solitarius (NTS) dorsal motor nucleus of the vagus (DMV) and area postrema) decrease gastric tone and motility. Our first aim was to investigate the mechanism(s) of OXT-induced gastric relaxation. We demonstrated recently that vagal afferent inputs modulate NTS-DMV synapses involved in gastric and pancreatic reflexes via group II metabotropic glutamate receptors (mGluRs). Our second aim was to investigate whether group II mGluRs similarly influence the response of vagal motoneurons to OXT. Microinjection of OXT in the DVC decreased gastric tone in a dose-dependent manner. The OXT-induced gastric relaxation was enhanced following bethanechol and reduced by l-NAME administration, suggesting a nitrergic mechanism of gastroinhibition. DVC application of the group II mGluR antagonist EGLU induced a gastroinhibition that was not dose dependent and shifted the gastric effects of OXT to a cholinergic-mediated mechanism. Evoked and miniature GABAergic synaptic currents between NTS and identified gastric-projecting DMV neurones were not affected by OXT in any neurones tested, unless the brainstem slice was (a) pretreated with EGLU or (b) derived from rats that had earlier received a surgical vagal deafferentation. Conversely, OXT inhibited glutamatergic currents even in naive slices, but their responses were unaffected by EGLU pretreatment. These results suggest that the OXT-induced gastroinhibition is mediated by activation of the NANC pathway. Inhibition of brainstem group II mGluRs, however, uncovers the ability of OXT to modulate GABAergic transmission between the NTS and DMV, resulting in the engagement of an otherwise silent cholinergic vagal neurocircuit.
authors.affiliation: Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, MC H109, Hershey, PA 17033, USA.
authors.forename: Gregory M
authors.initials: GM
authors.lastname: Holmes
authors.forename: Kirsteen N
authors.initials: KN
authors.lastname: Browning
authors.forename: Tanja
authors.initials: T
authors.lastname: Babic
authors.forename: Samuel R
authors.initials: SR
authors.lastname: Fortna
authors.forename: F Holly
authors.initials: FH
authors.lastname: Coleman
authors.forename: R Alberto
authors.initials: RA
authors.lastname: Travagli
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D018723:Bethanechol / Q000494:pharmacology; D018680:Cholinergic Antagonists / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D059330:GABAergic Neurons / Q000502:physiology; D005769:Gastrointestinal Motility / Q000187:drug effects*; D009046:Motor Neurons / Q000502:physiology; D018721:Muscarinic Agonists / Q000494:pharmacology; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009475:Neurons, Afferent / Q000502:physiology*; D010121:Oxytocin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012018:Reflex / Q000187:drug effects; D017552:Solitary Nucleus / Q000502:physiology; D013270:Stomach / Q000294:innervation / Q000502:physiology*; D013569:Synapses / Q000502:physiology; D009435:Synaptic Transmission / Q000187:drug effects; D014630:Vagus Nerve / Q000502:physiology*
chemical_list: D018680:Cholinergic Antagonists; D018691:Excitatory Amino Acid Antagonists; D018721:Muscarinic Agonists; D018723:Bethanechol; D010121:Oxytocin; D019331:NG-Nitroarginine Methyl Ester