Glucagon-like peptide-2 modulates neurally evoked mucosal chloride secretion in guinea pig small intestine in vitro
Open accessAbstract
Glucagon-like peptide-2 (GLP-2) is an important neuroendocrine peptide in intestinal physiology. It influences digestion, absorption, epithelial growth, motility, and blood flow. We studied involvement of GLP-2 in intestinal mucosal secretory behavior. Submucosal-mucosal preparations from guinea pig ileum were mounted in Ussing chambers for measurement of short-circuit current ( I sc) as a surrogate for chloride secretion. GLP-2 action on neuronal release of acetylcholine was determined with ELISA. Enteric neuronal expression of the GLP-2 receptor (GLP-2R) was studied with immunohistochemical methods. Application of GLP-2 (0.1–100 nM) to the serosal or mucosal side of the preparations evoked no change in baseline I sc and did not alter transepithelial ionic conductance. Transmural electrical field stimulation (EFS) evoked characteristic biphasic increases in I sc, with an initially rapid rising phase followed by a sustained phase. Application of GLP-2 reduced the EFS-evoked biphasic responses in a concentration-dependent manner. The GLP-2R antagonist GLP-2-(3-33) significantly reversed suppression of the EFS-evoked responses by GLP-2. Tetrodotoxin, scopolamine, and hexamethonium, but not vasoactive intestinal peptide type 1 receptor (VPAC1) antagonist abolished or reduced to near zero the EFS-evoked responses. GLP-2 suppressed EFS-evoked acetylcholine release as measured by ELISA. Pretreatment with GLP-2-(3-33) offset this action of GLP-2. In the submucosal plexus, GLP-2R immunoreactivity (-IR) was expressed in choline acetyltransferase-IR neurons, somatostatin-IR neurons, neuropeptide Y-IR neurons, and vasoactive intestinal peptide-IR neurons. We conclude that submucosal neurons in the guinea pig ileum express GLP-2R. Activation of GLP-2R decreases neuronally evoked epithelial chloride secretion by suppressing acetylcholine release from secretomotor neurons.
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GLP-2 receptors are present on enteric neurons in guinea pig ileum, mouse jejunum, mouse and pig intestine, and absorptive enterocyte progenitors in mouse jejunum respond to GLP-2 in an enteric neuron-dependent manner.
“Indeed, GLP-2 receptors are present on enteric neurons in guinea pig ileum, mouse jejunum, mouse and pig intestine (20,51,52) and absorptive enterocyte progenitors in mouse jejunum respond to GLP-2 in an enteric neuron-dependent manner (52).”
From Gut mechanisms linking intestinal sweet sensing to glycemic control (2018) · cites this paper as [51]
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- Authors
- Baldassano, S., Liu, S., Qu, M.-H., Mulè, F., & Wood, J. D.
- Affiliations
- Departments of Physiology and Cell Biology and
- The Ohio State University Wexner Medical Center (US)
- Corresponding author
- Wood, Jackie D.
- Venue
- American Journal of Physiology-Gastrointestinal and Liver Physiology
- Publisher
- American Physiological Society
- Published
- 2009-10
- Volume
- 297
- Issue
- 4
- Pages
- G800-G805
- ISSN
- 0193-1857 (ISSN-L)
- 1522-1547
- PMC
- PMC2763802
- OpenAlex
- W2136623260
- Cited by
- 56
- References
- 38
- Citations by year
- 2025: 3 · 2021: 2 · 2020: 2 · 2019: 5 · 2018: 8 · 2017: 2 · 2016: 9 · 2015: 4 · 2014: 3 · 2013: 1 · 2012: 8
- FWCI
- 2.32
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- American Journal of Physiology-Gastrointestinal and Liver Physiology (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- IRIS UniPA (University of Palermo) (submittedVersion, other-oa)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK037238, R01DK057075)
- Topics
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuropeptides and Animal Physiology
- Health Sciences › Medicine › Gastroenterology › Gastrointestinal motility and disorders
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Keywords
- glucagon-like peptide-2, GLP-2 receptor, intestinal chloride secretion, acetylcholine release, secretomotor neurons, enteric nervous system, submucosal plexus, electrical field stimulation, ileum, cholinergic neurons, somatostatin neurons, neuropeptide Y neurons, vasoactive intestinal peptide neurons, short-circuit current
- MeSH terms
- Glucagon-Like Peptide-2 Receptor, Acetylcholine, Animals, Chlorides, Choline O-Acetyltransferase, Electric Stimulation, Enzyme-Linked Immunosorbent Assay, Fluorescent Antibody Technique, Guinea Pigs, Ileum, Immunohistochemistry, Intestinal Mucosa, Intestinal Secretions, Male, Membrane Potentials, Neuropeptide Y, Somatostatin, Time Factors, Vasoactive Intestinal Peptide, Enteric Nervous System, Receptors, Glucagon, Neurotransmitter Agents, Glucagon-Like Peptide 2, In Vitro Techniques
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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