Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor nucleus of the vagus neurones to group II metabotropic glutamate receptor agonists in rats.
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. In control rats, microinjection of bicuculline into the DMV increased PES, whereas microinjections of kynurenic acid had no effect. Conversely, in AP rats, microinjection of bicuculline had no effect, whereas kynurenic acid decreased PES. DMV microinjections of the group II mGluR agonist APDC and whole cell recordings of excitatory currents in identified pancreas-projecting DMV neurones showed a reduced functional response in AP rats compared to controls. Moreover, these changes persisted up to 3 weeks following the induction of AP. These data demonstrate that AP increases the excitatory input to pancreas-projecting DMV neurones by decreasing the response of excitatory synaptic terminals to group II mGluR agonist.
Department of Neural and Behavioral Sciences, Penn State College of Medicine, 500 University Drive, MC H109, Hershey, PA 17033, USA. rtravagli@hmc.psu.edu.
Tanja
T
Babic
R Alberto
RA
Travagli
D000818:Animals; D001640:Bicuculline / Q000008:administration & dosage; D018690:Excitatory Amino Acid Agonists / Q000008:administration & dosage; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D058787:GABA-A Receptor Antagonists / Q000008:administration & dosage; D053444:Inhibitory Postsynaptic Potentials / Q000187:drug effects / Q000502:physiology; D007736:Kynurenic Acid / Q000008:administration & dosage; D008297:Male; D008526:Medulla Oblongata / Q000187:drug effects / Q000503:physiopathology; D008845:Microinjections; D009046:Motor Neurons / Q000502:physiology; D046790:Pancreas, Exocrine / Q000187:drug effects / Q000294:innervation* / Q000503:physiopathology; D010195:Pancreatitis / Q000503:physiopathology*; D011422:Propionates / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists*; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology; D014630:Vagus Nerve / Q000187:drug effects* / Q000503:physiopathology*
C114785:2-amino-4-phosphono-propinate; D018690:Excitatory Amino Acid Agonists; D058787:GABA-A Receptor Antagonists; D011422:Propionates; D018094:Receptors, Metabotropic Glutamate; C108822:metabotropic glutamate receptor 2; D007736:Kynurenic Acid; D001640:Bicuculline