Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor nucleus of the vagus neurones to group II metabotropic glutamate receptor agonists in rats
Acute pancreatitis decreases the sensitivity of pancreas-projecting dorsal motor nucleus of the vagus neurones to group II metabotropic glutamate receptor agonists in rats
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DOI：
10.1113/jphysiol.2013.270108
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发表时间：
2014-03-15
影响因子：
5.5
通讯作者：
Travagli, R. Alberto
中科院分区：
文献类型：
--
作者：
Babic, Tanja;Travagli, R. Alberto
急性胰腺炎是最严重的胰腺外分泌疾病之一。胰腺外分泌(PES)受迷走神经背侧运动核(DMV)神经元的调节，其活性受抑制性GABA能和兴奋性谷氨酸能突触输入的调节。第二组代谢性谷氨酸受体(MGluR)减少突触向胰腺投射DMV神经元的突触传递，并调节PES。我们的研究表明，急性胰腺炎通过降低兴奋性突触终末对II组mGluR激动剂的反应，导致兴奋性突触传递到胰腺投射神经元的持久增加。这些数据表明，DMV中II组mGluR表达的变化可能是急性胰腺炎PES短期和长期变化的基础。最近的研究表明，胰腺外分泌(PES)受到迷走神经背核(DMV)神经元的调节，其活动受到GABA能和谷氨酸能突触输入的微调。第二组代谢性谷氨酸受体(MGluR)减少突触向胰腺投射的DMV神经元的传递，增加PES。在本研究中，我们采用体内和体外相结合的方法，旨在表征雨蛙素诱导的急性胰腺炎(AP)对调节胰腺功能的迷走神经回路的影响。在对照组大鼠中，DMV内微量注射荷包牡丹碱可增加PES，而微量注射犬尿酸则不起作用。相反，在AP大鼠，微量注射荷包牡丹碱不起作用，而犬尿酸则降低PES。DMV微量注射II组mGluR激动剂APDC和对已识别的胰腺投射DMV神经元兴奋电流的全细胞记录显示，与对照组相比，AP大鼠的功能反应减弱。此外，这些变化在AP诱导后持续到3周。这些数据表明，AP通过降低兴奋性突触终末对II组mGluR激动剂的反应，增加了对胰腺投射的DMV神经元的兴奋性输入。
Key pointsAcute pancreatitis is one of the most severe disorders of the exocrine pancreas.Pancreatic exocrine secretions (PES) are under regulatory control of dorsal motor nucleus of the vagus (DMV) neurones and their activity is regulated by inhibitory GABAergic and excitatory glutamatergic synaptic inputs.Group II metabotropic glutamate receptors (mGluR) decrease synaptic transmission to pancreas-projecting DMV neurones and modulate PES.In this study, we show that acute pancreatitis induces a long-lasting increase in excitatory synaptic transmission to pancreas-projecting neurones by decreasing the response of excitatory synaptic terminals to group II mGluR agonists.These data suggest that changes in group II mGluR expression in the DMV may underlie short- and long-term changes in PES in acute pancreatitis.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.