Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

V Bucinskaite; T Tolessa; J Pedersen; B Rydqvist; L Zerihun; Jens Juul Holst; P M Hellström

doi:10.1111/j.1365-2982.2009.01317.x

Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

V Bucinskaite, T Tolessa, J Pedersen, B Rydqvist, L Zerihun, Jens Juul Holst, P M Hellström

Endocrinology and Metabolism

89 Citations (Scopus)

Abstract

The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.

Original language	English
Journal	Neurogastroenterology and Motility
Volume	21
Issue number	9
Pages (from-to)	978-e78
ISSN	1350-1925
DOIs	https://doi.org/10.1111/j.1365-2982.2009.01317.x
Publication status	Published - 2009

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10.1111/j.1365-2982.2009.01317.x

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@article{6d513700335511df8ed1000ea68e967b,

title = "Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat",

abstract = "The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.",

author = "V Bucinskaite and T Tolessa and J Pedersen and B Rydqvist and L Zerihun and Holst, {Jens Juul} and Hellstr{\"o}m, {P M}",

note = "Keywords: Animals; Dose-Response Relationship, Drug; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hydrochloric Acid; Injections, Intravenous; Male; Neurons, Afferent; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Glucagon; Stomach; Vagus Nerve",

year = "2009",

doi = "10.1111/j.1365-2982.2009.01317.x",

language = "English",

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pages = "978--e78",

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T1 - Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

AU - Bucinskaite, V

AU - Tolessa, T

AU - Pedersen, J

AU - Rydqvist, B

AU - Zerihun, L

AU - Holst, Jens Juul

AU - Hellström, P M

N1 - Keywords: Animals; Dose-Response Relationship, Drug; Glucagon-Like Peptide 1; Glucagon-Like Peptide 2; Hydrochloric Acid; Injections, Intravenous; Male; Neurons, Afferent; Peptide Fragments; Rats; Rats, Sprague-Dawley; Receptors, Glucagon; Stomach; Vagus Nerve

PY - 2009

Y1 - 2009

N2 - The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.

AB - The vagus nerve plays a role in mediating effects of the two glucagon-like peptides GLP-1 and GLP-2 on gastrointestinal growth, functions and eating behaviour. To obtain electrophysiological and molecular evidence for the contribution of afferent pathways in chemoreception from the gastrointestinal tract, afferent mass activity in the ventral gastric branch of the vagus nerve and gene expression of GLP-1 receptors and GLP-2 receptors in the nodose ganglion were examined in Sprague-Dawley rats. Intravenous administration of GLP-1 (30-1000 pmol kg(-1)), reaching high physiological plasma concentrations, increased vagal afferent mass activity peaking (13-52% above basal level, P < 0.05) 3-5 min after injection. Repeated administration of GLP-1 (1000 pmol kg(-1); five times, 15 min intervals) elicited similar responses. Pretreatment with GLP-1 receptor antagonist exendin(9-39)amide (500 pmol kg(-1)) abolished the GLP-1 response to doses 30-300 pmol kg(-1) but had no effect on the vagal response to gastric distension. For comparison, GLP-2 (1000 pmol kg(-1)) had no effect on vagal afferent activity. Vagal chemoreception of GLP-1 is supported by expression of the GLP-1 receptor gene in the nodose ganglion. However, the GLP-2 receptor was also expressed. To conclude, our results show that peripherally administered GLP-1, differently from GLP-2, activates vagal afferents, with no evidence of desensitisation. The GLP-1 effect was blocked by exendin(9-39)amide, suggesting that GLP-1 receptors on vagal afferent nerves mediate sensory input from the gastrointestinal tract or pancreas; either directly or indirectly via the release of another mediator. GLP-2 receptors appear not be functionally expressed on vagal afferents.

U2 - 10.1111/j.1365-2982.2009.01317.x

DO - 10.1111/j.1365-2982.2009.01317.x

M3 - Journal article

C2 - 19453518

SN - 1350-1925

VL - 21

SP - 978-e78

JO - Neurogastroenterology and Motility

JF - Neurogastroenterology and Motility

IS - 9

ER -

Receptor-mediated activation of gastric vagal afferents by glucagon-like peptide-1 in the rat

Abstract

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