title: Glucagon-like peptide-1 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro.
abstract: Glucagon-like peptide-1 (GLP-1) acts at the G protein-coupled receptor, GLP-1R, to stimulate secretion of insulin and to inhibit secretion of glucagon and gastric acid. Involvement in mucosal secretory physiology has received negligible attention. We aimed to study involvement of GLP-1 in mucosal chloride secretion in the small intestine. Ussing chamber methods, in concert with transmural electrical field stimulation (EFS), were used to study actions on neurogenic chloride secretion. ELISA was used to study GLP-1R effects on neural release of acetylcholine (ACh). Intramural localization of GLP-1R was assessed with immunohistochemistry. Application of GLP-1 to serosal or mucosal sides of flat-sheet preparations in Ussing chambers did not change baseline short-circuit current (I(sc)), which served as a marker for chloride secretion. Transmural EFS evoked neurally mediated biphasic increases in I(sc) that had an initial spike-like rising phase followed by a sustained plateau-like phase. Blockade of the EFS-evoked responses by tetrodotoxin indicated that the responses were neurally mediated. Application of GLP-1 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-1 receptor antagonist exendin-(9-39) suppressed this action of GLP-1. The GLP-1 inhibitory action on EFS-evoked responses persisted in the presence of nicotinic or vasoactive intestinal peptide receptor antagonists but not in the presence of a muscarinic receptor antagonist. GLP-1 significantly reduced EFS-evoked ACh release. In the submucosal plexus, GLP-1R immunoreactivity (IR) was expressed by choline acetyltransferase-IR neurons, neuropeptide Y-IR neurons, somatostatin-IR neurons, and vasoactive intestinal peptide-IR neurons. Our results suggest that GLP-1R is expressed in guinea pig submucosal neurons and that its activation leads to a decrease in neurally evoked chloride secretion by suppressing release of ACh at neuroepithelial junctions in the enteric neural networks that control secretomotor functions.
authors.affiliation: Department of Physiology and Cell Biology, The Ohio State University College of Medicine, Columbus, Ohio, USA.
authors.forename: Sara
authors.initials: S
authors.lastname: Baldassano
authors.forename: Guo-Du
authors.initials: GD
authors.lastname: Wang
authors.forename: Flavia
authors.initials: F
authors.lastname: Mulè
authors.forename: Jackie D
authors.initials: JD
authors.lastname: Wood
mesh_terms: D000109:Acetylcholine / Q000378:metabolism; D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002712:Chlorides / Q000378:metabolism*; D002795:Choline O-Acetyltransferase / Q000378:metabolism; D003593:Cytoplasm / Q000378:metabolism; D051959:ELAV Proteins / Q000378:metabolism; D004553:Electric Conductivity; D004558:Electric Stimulation; D055724:Electrophysiological Phenomena / Q000187:drug effects / Q000502:physiology; D052216:Glucagon-Like Peptide 1 / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000067757:Glucagon-Like Peptide-1 Receptor; D006168:Guinea Pigs; D018738:Hexamethonium / Q000494:pharmacology; D007082:Ileum / Q000187:drug effects / Q000294:innervation / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000187:drug effects / Q000294:innervation* / Q000378:metabolism*; D007421:Intestine, Small / Q000187:drug effects / Q000294:innervation / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D009478:Neuropeptide Y / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology; D018027:Receptors, Glucagon / Q000378:metabolism; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I / Q000037:antagonists & inhibitors; D012601:Scopolamine / Q000494:pharmacology; D013004:Somatostatin / Q000378:metabolism; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism / Q000494:pharmacology
chemical_list: D002712:Chlorides; D051959:ELAV Proteins; D000067757:Glucagon-Like Peptide-1 Receptor; D009478:Neuropeptide Y; D010446:Peptide Fragments; D018027:Receptors, Glucagon; D051238:Receptors, Vasoactive Intestinal Polypeptide, Type I; D014660:Vasoactive Intestinal Peptide; D018738:Hexamethonium; D013004:Somatostatin; C083773:exendin (9-39); D052216:Glucagon-Like Peptide 1; D002217:Carbachol; D012601:Scopolamine; D002795:Choline O-Acetyltransferase; D000109:Acetylcholine
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