Using a brainstem slice preparation, we aimed to study the pre- and postsynaptic effects of glucagon-like peptide-1 (GLP-1) on synaptic transmission to identified pancreas-projecting vagal motoneurons. Following blockade of GABAergic mediated currents with bicuculline, perfusion with 100 nM GLP-1 increased both amplitude and frequency of excitatory postsynaptic currents (EPSCs) in 21 of 52 neurons. Perfusion with the GLP-1 selective agonist exendin-4 (100 nM), also increased the frequency of spontaneous EPSCs, while pretreatment with the GLP-1 selective antagonist, exendin 9-39, prevented the effects of GLP-1. In the presence of kynurenic acid to block ionotropic glutamatergic currents, perfusion with GLP-1 increased the frequency of inhibitory postsynaptic currents (IPSCs) in 28 of 74 neurons; in 14 of these responsive neurons, GLP-1 also increased IPSC amplitude, indicating actions at both pre- and postsynaptic sites. Perfusion with exendin-4 increased the frequency of spontaneous IPSCs, while pretreatment with exendin 9-39 prevented the effects of GLP-1. These results suggest that GLP-1 modulates both excitatory and inhibitory synaptic inputs to pancreas-projecting vagal motoneurons.
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http://dx.doi.org/10.1016/j.peptides.2007.08.016 | DOI Listing |
Dev Cell
January 2025
Department of Cell Biology and Anatomy, New York Medical College, Valhalla, NY 01595, USA; Department of Pharmacology, New York Medical College, Valhalla, NY 10595, USA. Electronic address:
Vagal nerve stimulation has emerged as a promising modality for treating a wide range of chronic conditions, including metabolic disorders. However, the cellular and molecular pathways driving these clinical benefits remain largely obscure. Here, we demonstrate that fibroblast growth factor 3 (Fgf3) mRNA is upregulated in the mouse vagal ganglia under acute metabolic stress.
View Article and Find Full Text PDFJ Physiol
March 2014
Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, MC H109, Hershey, PA 17033, USA.
Recent studies have shown that pancreatic exocrine secretions (PES) are modulated by dorsal motor nucleus of the vagus (DMV) neurones, whose activity is finely tuned by GABAergic and glutamatergic synaptic inputs. Group II metabotropic glutamate receptors (mGluR) decrease synaptic transmission to pancreas-projecting DMV neurones and increase PES. In the present study, we used a combination of in vivo and in vitro approaches aimed at characterising the effects of caerulein-induced acute pancreatitis (AP) on the vagal neurocircuitry modulating pancreatic functions.
View Article and Find Full Text PDFCurr Opin Gastroenterol
September 2013
Department of Medicine, Duke University Medical Center, Durham, NC 27710, USA.
Purpose Of Review: Recent advances in the regulation of pancreatic secretion by secretagogues, modulatory proteins and neural pathways are discussed.
Recent Findings: Downstream events involved in secretagogue stimulation of pancreatic secretion have been elucidated through characterization of the Src kinase pathway. An additional mechanism regulating vagus nerve effects on the pancreas involves Group II and III metabotropic glutamate receptors that are located presynaptically on certain vagal pancreas-projecting neurons.
J Physiol
August 2012
Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, MC H109, Hershey, PA 17033, USA.
Brainstem vago-vagal neurocircuits modulate upper gastrointestinal functions. Derangement of these sensory-motor circuits is implicated in several pathophysiological states, such as gastroesophageal reflux disease (GERD), functional dyspepsia and, possibly, pancreatitis. While vagal circuits controlling the stomach have received more attention, the organization of brainstem pancreatic neurocircuits is still largely unknown.
View Article and Find Full Text PDFPeptides
November 2007
Research Center of Digestive Diseases, Zhongnan Hospital, Key Laboratory of Allergy and Immune-related Diseases, Department of Physiology, School of Basic Medical Science, Wuhan University, Wuhan, Hubei 430071, PR China.
Using a brainstem slice preparation, we aimed to study the pre- and postsynaptic effects of glucagon-like peptide-1 (GLP-1) on synaptic transmission to identified pancreas-projecting vagal motoneurons. Following blockade of GABAergic mediated currents with bicuculline, perfusion with 100 nM GLP-1 increased both amplitude and frequency of excitatory postsynaptic currents (EPSCs) in 21 of 52 neurons. Perfusion with the GLP-1 selective agonist exendin-4 (100 nM), also increased the frequency of spontaneous EPSCs, while pretreatment with the GLP-1 selective antagonist, exendin 9-39, prevented the effects of GLP-1.
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