GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow
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GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow. / Guan, Xinfu; Karpen, Heidi E; Stephens, John; Bukowski, John T; Niu, Sanyong; Zhang, Guangcheng; Stoll, Barbara; Finegold, Milton J; Holst, Jens Juul; Hadsell, Darryl; Hadsell, Darry L; Nichols, Buford L; Burrin, Douglas G.
In: Gastroenterology, Vol. 130, No. 1, 01.2006, p. 150-64.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - GLP-2 receptor localizes to enteric neurons and endocrine cells expressing vasoactive peptides and mediates increased blood flow
AU - Guan, Xinfu
AU - Karpen, Heidi E
AU - Stephens, John
AU - Bukowski, John T
AU - Niu, Sanyong
AU - Zhang, Guangcheng
AU - Stoll, Barbara
AU - Finegold, Milton J
AU - Holst, Jens Juul
AU - Hadsell, Darryl
AU - Hadsell, Darry L
AU - Nichols, Buford L
AU - Burrin, Douglas G
PY - 2006/1
Y1 - 2006/1
N2 - BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive hormone that exerts diverse actions in the gastrointestinal tract, including enhancing epithelial cell survival and proliferation, mucosal blood flow, and nutrient uptake and suppressing gastric motility and secretion. These actions are mediated by the G-protein-coupled receptor, GLP-2R. Cellular localization of the GLP-2R and the nature of its signaling network in the gut, however, are poorly defined. Thus, our aim was to establish cellular localization of GLP-2R and functional connection to vascular action of GLP-2 in the gut.METHODS: Intestinal cellular GLP-2R localization was determined with real-time, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) of laser capture microdissected subtissue and fluorescence in situ hybridization and also with double and/or triple immunostaining of human and pig tissue using a validated GLP-2R polyclonal antibody. Superior mesenteric arterial blood flow and intestinal eNOS expression and phosphorylation were measured in TPN-fed pigs acutely (4 h) infused with GLP-2.RESULTS: We show that the porcine GLP-2R mRNA was expressed in the villus epithelium and myenteric plexus. GLP-2R protein was co-localized by confocal immunohistochemistry with serotonin in enteroendocrine cells and also with endothelial nitric oxide synthase (eNOS)-expressing and vasoactive intestinal polypeptide-positive enteric neurons. In neonatal pigs, GLP-2 infusion dose-dependently stimulated intestinal blood flow and coordinately upregulated the expression of intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117).CONCLUSIONS: We conclude that the GLP-2-induced stimulation of blood flow is mediated by vasoactive neurotransmitters that are colocalized with GLP-2R in 2 functionally distinct cell types within the gastrointestinal tract.
AB - BACKGROUND & AIMS: Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive hormone that exerts diverse actions in the gastrointestinal tract, including enhancing epithelial cell survival and proliferation, mucosal blood flow, and nutrient uptake and suppressing gastric motility and secretion. These actions are mediated by the G-protein-coupled receptor, GLP-2R. Cellular localization of the GLP-2R and the nature of its signaling network in the gut, however, are poorly defined. Thus, our aim was to establish cellular localization of GLP-2R and functional connection to vascular action of GLP-2 in the gut.METHODS: Intestinal cellular GLP-2R localization was determined with real-time, quantitative reverse-transcription polymerase chain reaction (qRT-PCR) of laser capture microdissected subtissue and fluorescence in situ hybridization and also with double and/or triple immunostaining of human and pig tissue using a validated GLP-2R polyclonal antibody. Superior mesenteric arterial blood flow and intestinal eNOS expression and phosphorylation were measured in TPN-fed pigs acutely (4 h) infused with GLP-2.RESULTS: We show that the porcine GLP-2R mRNA was expressed in the villus epithelium and myenteric plexus. GLP-2R protein was co-localized by confocal immunohistochemistry with serotonin in enteroendocrine cells and also with endothelial nitric oxide synthase (eNOS)-expressing and vasoactive intestinal polypeptide-positive enteric neurons. In neonatal pigs, GLP-2 infusion dose-dependently stimulated intestinal blood flow and coordinately upregulated the expression of intestinal eNOS mRNA, protein, and phosphorylation (eNOS-Ser1117).CONCLUSIONS: We conclude that the GLP-2-induced stimulation of blood flow is mediated by vasoactive neurotransmitters that are colocalized with GLP-2R in 2 functionally distinct cell types within the gastrointestinal tract.
KW - Animals
KW - Enteroendocrine Cells
KW - Female
KW - Humans
KW - Immunohistochemistry
KW - In Situ Hybridization, Fluorescence
KW - Intestine, Small
KW - Mesenteric Arteries
KW - Neurons
KW - Nitric Oxide Synthase Type III
KW - RNA, Messenger
KW - Receptors, Glucagon
KW - Regional Blood Flow
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Swine
KW - Vasoactive Intestinal Peptide
U2 - 10.1053/j.gastro.2005.11.005
DO - 10.1053/j.gastro.2005.11.005
M3 - Journal article
C2 - 16401478
VL - 130
SP - 150
EP - 164
JO - Gastroenterology
JF - Gastroenterology
SN - 0016-5085
IS - 1
ER -
ID: 132053190