Group III metabotropic glutamate receptors activate selectively pancreas‐projecting neurons in the dorsal motor nucleus of the vagus that control endocrine secretions

Abstract

We have shown that pancreas‐projecting vagal preganglionic neurons (DMV) can be distinguished as exocrine vs endocrine‐controlling based on their response to either cholecystokinin (CCK) and pancreatic polypeptide (PP) or glucagon‐like peptide‐1 (GLP‐1), respectively. We have also shown that the group III metabotropic glutamate receptors (mGluR) agonist L‐AP4 decreases synaptic inputs to pancreas‐projecting DMV neurons. However, in an in vivo preparation, microinjections of L‐AP4 into the DMV have no effect on pancreatic exocrine secretion.Here we aim to determine whether L‐AP4 can be used to distinguish central vagal circuits controlling pancreatic exocrine vs endocrine secretions.Whole‐cell patch‐clamp recordings in identified pancreas‐projecting rat DMV neurons show that perfusion with L‐AP4 (100μM) decreased the frequency of miniature excitatory postsynaptic currents in 8/9 neurons tested. None of the L‐AP4‐responsive neurons responded to CCK (100 nM) and 1/5 neurons tested responded to PP (100 nM). In contrast, 4/5 L‐AP4‐responsive neurons also responded to GLP‐1 (100 nM).Since CCK and PP regulate exocrine‐, whereas GLP‐1 regulates endocrine‐pancreatic secretions, our findings support the hypothesis that distinct central vagal circuits control exocrine vs endocrine secretions and suggest that activation of group III mGluRs in the DMV regulates selectively endocrine functions.Supported by: NSF IBN‐104‐9618 to AT