Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.

Antonella Amato, Rosa Maria Serio, Flavia Mule', Cinci, Vannucchi, Faussone-Pellegrini

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Abstract

Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinalmotility through vagal afferents and central nervousmechanisms; however, no data is available about adirect influence on the gastrointestinal wall. Our aimwas to investigate the effects of GLP-1 on thespontaneous and evoked mechanical activity ofmouse duodenum and colon and to identify thepresence and distribution of GLP-1 receptors (GLP-1R)in the muscle coat. Methods Organ bath recordingtechnique and immunohistochemistry were used.Key Results Glucagon-like peptide-1 (up to the concentrationof 1 lmol L)1) failed to affect spontaneousmechanical activity. It caused concentration-dependentreduction of the electrically evoked cholinergiccontractions in circular smooth muscle of both intestinalsegments, without affecting the longitudinalmuscle responses. Glucagon-like peptide-1 inhibitoryeffect was significantly antagonized by exendin (9–39),an antagonist of GLP-1R. In both intestinal preparations,GLP-1 effect was not affected by guanethidine, ablocker of adrenergic neurotransmission, but it wassignificantly reduced by Nx-nitro-L-arginine methylester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractionsevoked by exogenous carbachol. Immunohistochemistrydemonstrated GLP-1R expression in the entericneurons. Furthermore, 27% of GLP-1R immunoreactive(IR) neurons in the duodenum and 79% of GLP-1R-IR neurons in the colon, co-expressed nNOS.Conclusions & Inferences The present results suggestthat GLP-1 is able to act in the enteric nervous systemby decreasing the excitatory cholinergic neurotransmissionthrough presynaptic GLP-1Rs, which modulateNO release.
Lingua originaleEnglish
pagine (da-a)664-672
Numero di pagine9
RivistaNeurogastroenterology and Motility
Volume22
Stato di pubblicazionePublished - 2010

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Glucagon-Like Peptide 1
Enteroendocrine Cells
Duodenum
Colon
Proglucagon
Neurons
Guanethidine
Large Intestine
Carbachol
Baths
Nitric Oxide Synthase
Synaptic Transmission
Adrenergic Agents
Cholinergic Agents
Small Intestine
Smooth Muscle
Meals
Arginine
Eating
Immunohistochemistry

All Science Journal Classification (ASJC) codes

  • Physiology
  • Endocrine and Autonomic Systems
  • Gastroenterology

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@article{fe601e6144114597be66cbb9b59d52c3,
title = "Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.",
abstract = "Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinalmotility through vagal afferents and central nervousmechanisms; however, no data is available about adirect influence on the gastrointestinal wall. Our aimwas to investigate the effects of GLP-1 on thespontaneous and evoked mechanical activity ofmouse duodenum and colon and to identify thepresence and distribution of GLP-1 receptors (GLP-1R)in the muscle coat. Methods Organ bath recordingtechnique and immunohistochemistry were used.Key Results Glucagon-like peptide-1 (up to the concentrationof 1 lmol L)1) failed to affect spontaneousmechanical activity. It caused concentration-dependentreduction of the electrically evoked cholinergiccontractions in circular smooth muscle of both intestinalsegments, without affecting the longitudinalmuscle responses. Glucagon-like peptide-1 inhibitoryeffect was significantly antagonized by exendin (9–39),an antagonist of GLP-1R. In both intestinal preparations,GLP-1 effect was not affected by guanethidine, ablocker of adrenergic neurotransmission, but it wassignificantly reduced by Nx-nitro-L-arginine methylester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractionsevoked by exogenous carbachol. Immunohistochemistrydemonstrated GLP-1R expression in the entericneurons. Furthermore, 27{\%} of GLP-1R immunoreactive(IR) neurons in the duodenum and 79{\%} of GLP-1R-IR neurons in the colon, co-expressed nNOS.Conclusions & Inferences The present results suggestthat GLP-1 is able to act in the enteric nervous systemby decreasing the excitatory cholinergic neurotransmissionthrough presynaptic GLP-1Rs, which modulateNO release.",
keywords = "GI hormones, acetylcholine, colon, duodenum, enteric nervous system, immunohistochemistry, nitric oxide.",
author = "Antonella Amato and Serio, {Rosa Maria} and Flavia Mule' and Cinci and Vannucchi and Faussone-Pellegrini",
year = "2010",
language = "English",
volume = "22",
pages = "664--672",
journal = "Neurogastroenterology and Motility",
issn = "1350-1925",
publisher = "Wiley-Blackwell",

}

TY - JOUR

T1 - Peripheral motor action of glucagon-like peptide-1 through enteric neuronal receptors.

AU - Amato, Antonella

AU - Serio, Rosa Maria

AU - Mule', Flavia

AU - Cinci, null

AU - Vannucchi, null

AU - Faussone-Pellegrini, null

PY - 2010

Y1 - 2010

N2 - Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinalmotility through vagal afferents and central nervousmechanisms; however, no data is available about adirect influence on the gastrointestinal wall. Our aimwas to investigate the effects of GLP-1 on thespontaneous and evoked mechanical activity ofmouse duodenum and colon and to identify thepresence and distribution of GLP-1 receptors (GLP-1R)in the muscle coat. Methods Organ bath recordingtechnique and immunohistochemistry were used.Key Results Glucagon-like peptide-1 (up to the concentrationof 1 lmol L)1) failed to affect spontaneousmechanical activity. It caused concentration-dependentreduction of the electrically evoked cholinergiccontractions in circular smooth muscle of both intestinalsegments, without affecting the longitudinalmuscle responses. Glucagon-like peptide-1 inhibitoryeffect was significantly antagonized by exendin (9–39),an antagonist of GLP-1R. In both intestinal preparations,GLP-1 effect was not affected by guanethidine, ablocker of adrenergic neurotransmission, but it wassignificantly reduced by Nx-nitro-L-arginine methylester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractionsevoked by exogenous carbachol. Immunohistochemistrydemonstrated GLP-1R expression in the entericneurons. Furthermore, 27% of GLP-1R immunoreactive(IR) neurons in the duodenum and 79% of GLP-1R-IR neurons in the colon, co-expressed nNOS.Conclusions & Inferences The present results suggestthat GLP-1 is able to act in the enteric nervous systemby decreasing the excitatory cholinergic neurotransmissionthrough presynaptic GLP-1Rs, which modulateNO release.

AB - Background Glucagon-like peptide-1 (GLP-1) is a proglucagon-derived peptide expressed in the enteroendocrine-L cells of small and large intestine and released in response to meal ingestion. Glucagon-like peptide-1 exerts inhibitory effects on gastrointestinalmotility through vagal afferents and central nervousmechanisms; however, no data is available about adirect influence on the gastrointestinal wall. Our aimwas to investigate the effects of GLP-1 on thespontaneous and evoked mechanical activity ofmouse duodenum and colon and to identify thepresence and distribution of GLP-1 receptors (GLP-1R)in the muscle coat. Methods Organ bath recordingtechnique and immunohistochemistry were used.Key Results Glucagon-like peptide-1 (up to the concentrationof 1 lmol L)1) failed to affect spontaneousmechanical activity. It caused concentration-dependentreduction of the electrically evoked cholinergiccontractions in circular smooth muscle of both intestinalsegments, without affecting the longitudinalmuscle responses. Glucagon-like peptide-1 inhibitoryeffect was significantly antagonized by exendin (9–39),an antagonist of GLP-1R. In both intestinal preparations,GLP-1 effect was not affected by guanethidine, ablocker of adrenergic neurotransmission, but it wassignificantly reduced by Nx-nitro-L-arginine methylester, inhibitor of nitric oxide (NO) synthase. Glucagon-like peptide-1 failed to affect the contractionsevoked by exogenous carbachol. Immunohistochemistrydemonstrated GLP-1R expression in the entericneurons. Furthermore, 27% of GLP-1R immunoreactive(IR) neurons in the duodenum and 79% of GLP-1R-IR neurons in the colon, co-expressed nNOS.Conclusions & Inferences The present results suggestthat GLP-1 is able to act in the enteric nervous systemby decreasing the excitatory cholinergic neurotransmissionthrough presynaptic GLP-1Rs, which modulateNO release.

KW - GI hormones

KW - acetylcholine

KW - colon

KW - duodenum

KW - enteric nervous system

KW - immunohistochemistry

KW - nitric oxide.

UR - http://hdl.handle.net/10447/51813

M3 - Article

VL - 22

SP - 664

EP - 672

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

SN - 1350-1925

ER -