|Burrin, Douglas - Doug|
Submitted to: Gastroenterology
Publication Type: Abstract Only
Publication Acceptance Date: 2/1/2005
Publication Date: 5/1/2005
Citation: Guan, X., Bukowski, J.T., Stephens, J., Niu, S., Zhang, G., Stoll, B., Karpen, H.E., Finegold, M.J., Holst, J.J., Hadsell, D.L., Nichols, B.L., Burrin, D.G. 2005. Glucagon-like peptide-2 receptor co-localization with vasoactive neurotransmitters in the human small intestine. Gastroenterology. Interpretive Summary: Interpretive Summary not needed for this 115.
Technical Abstract: Background & Aims: Glucagon-like peptide-2 (GLP-2) is a nutrient-responsive hormone that exerts diverse actions in the gastrointestinal tract including enhancing epithelial integrity, mucosal blood flow, 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 nature of its signaling network in the gut, however, is poorly defined. Thus, our aim was to establish the cellular localization of GLP-2R and functional connection with vascular action in the gut. Methods & Results: Using real-time qRT-PCR of laser capture microdissected sub-tissue and fluorescence in situ hybridization, we show that the porcine GLP-2R mRNA is expressed in villus epithelium and myenteric plexus. In human and pig tissue, double/triple immunostaining using a validated GLP-2R antibody demonstrated that the GLP-2R was co-localized with 5-HT in enteroendocrine cells and also with eNOS-expressing and VIP-positive enteric neurons. In neonatal pigs, GLP-2 infusion dose-dependently stimulates intestinal blood flow and coordinately up-regulates the expression of intestinal eNOS mRNA, protein, and phosphorylation. Conclusions: We conclude that the GLP-2R is colocalized with 5-HT, VIP and eNOS in functionally distinct cells within the enteric nervous system. The results suggest that 5-HT, VIP and NO may participate via enteric neurons as downstream GLP-2R signals in the regulation of intestinal blood flow.