RGD Reference Report - Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa. - Rat Genome Database

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Glucagon-like peptide-2 receptor activation in the rat intestinal mucosa.

Authors: Walsh, NA  Yusta, B  DaCambra, MP  Anini, Y  Drucker, DJ  Brubaker, PL 
Citation: Walsh NA, etal., Endocrinology. 2003 Oct;144(10):4385-92. Epub 2003 Jul 3.
RGD ID: 1627653
Pubmed: PMID:12960094   (View Abstract at PubMed)
DOI: DOI:10.1210/en.2003-0309   (Journal Full-text)

Glucagon-like peptide-2 (GLP-2) increases small intestinal growth and function in rodents and human subjects. GLP-2 exerts its effects through a seven-transmembrane domain, G protein-coupled receptor (GLP-2R), stimulating cAMP generation and activating protein kinase A signaling in heterologous cell lines transfected with the GLP-2R. As intestinal cell lines expressing the GLP-2R have not been identified, we developed methods for studying GLP-2R signaling in the rat small intestinal mucosa in vitro. Isolated rat intestinal mucosal cells expressed mRNA transcripts for the GLP-2R, as well as for chromogranin A and beta-tubulin III, markers for enteroendocrine and neural cells, respectively. cAMP production in response to [Gly2]GLP-2, a degradation-resistant analog of GLP-2, was maximal at 10-11 m (268 +/- 93% of control, P < 0.001), with reduced cAMP accumulation observed at higher doses. The cAMP response was diminished by pretreatment with 10-9 m GLP-2, and was abolished by pretreatment with 10-6 m GLP-2 (P < 0.05), indicating receptor desensitization. GLP-2 treatment of isolated mucosal cells increased 3H-thymidine incorporation (to 128 +/- 8% of controls, P < 0.05), and this was prevented by inhibition of the protein kinase A pathway with H89. In contrast, GLP-2 did not affect p44/p42 MAPK phosphorylation or the levels of cytosolic calcium in the mucosal cell preparation. These results provide the first evidence that activation of the endogenous rat mucosal GLP-2 receptor is linked to activation of a cAMP/protein kinase A-dependent, growth-promoting pathway in vitro.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Glp2rRatglucagon receptor activity  IDA  RGD 
GcgRatglucagon receptor binding  IDA  RGD 
GcgRathormone activity  IDA  RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gcg  (glucagon)
Glp2r  (glucagon-like peptide 2 receptor)


Additional Information