Premium
Vagally mediated effects of glucagon‐like peptide 1: in vitro and in vivo gastric actions
Author(s) -
Holmes Gregory M.,
Browning Kirsteen N.,
Tong Melissa,
QuallsCreekmore Emily,
Travagli R. Alberto
Publication year - 2009
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.2009.175067
Subject(s) - dorsal motor nucleus , bethanechol , medicine , endocrinology , agonist , chemistry , brainstem , vagotomy , vagus nerve , receptor , muscarinic acetylcholine receptor , biology , stimulation
Glucagon‐like peptide‐1 (GLP‐1) is a neuropeptide released following meal ingestion that, among other effects, decreases gastric tone and motility. The central targets and mechanism of action of GLP‐1 on gastric neurocircuits have not, however, been fully investigated. A high density of GLP‐1 containing neurones and receptors are present in brainstem vagal circuits, suggesting that the gastroinhibition may be vagally mediated. We aimed to investigate: (1) the response of identified gastric‐projecting neurones of the dorsal motor nucleus of the vagus (DMV) to GLP‐1 and its analogues; (2) the effects of brainstem application of GLP‐1 on gastric tone; and (3) the vagal pathway utilized by GLP‐1 to induce gastroinhibition. We conducted our experiments using whole‐cell recordings from identified gastric‐projecting DMV neurones and microinjection in the dorsal vagal complex (DVC) of anaesthetized rats while monitoring gastric tone. Perfusion with GLP‐1 induced a concentration‐dependent excitation of a subpopulation of gastric‐projecting DMV neurones. The GLP‐1 effects were mimicked by exendin‐4 and antagonized by exendin‐9–39. In an anaesthetized rat preparation, application of exendin‐4 to the DVC decreased gastric tone in a concentration‐dependent manner. The gastroinhibitory effects of exendin‐4 were unaffected by systemic pretreatment with the pro‐motility muscarinic agonist bethanechol, but were abolished by systemic administration of the nitric oxide synthase (NOS) inhibitor N G ‐nitro‐ l ‐arginine methyl ester ( l‐ NAME), or by bilateral vagotomy. Our data indicate that GLP‐1 activates selective receptors to excite DMV neurones mainly and that the gastroinhibition observed following application of GLP‐1 in the DVC is due to the activation of an inhibitory non‐adrenergic, non‐cholinergic input to the stomach.