Enteroendocrine localization of GLP-2 receptor expression in humans and rodents

Background & Aims: Glucagon-like peptide (GLP)-2, a product of the proglucagon gene, is expressed in enteroendocrine cells of the small and large intestine and is trophic to the gastrointestinal mucosa. GLP-2 also inhibits gastric acid secretion and emptying and upregulates intestinal hexose transport. GLP-2 acts via binding to a single G protein-coupled GLP-2 receptor (GLP-2R), but the cellular targets for the diverse actions of GLP-2 remain unknown. Methods: GLP-2R expression in rodent and human tissues was examined using a combination of Northern blotting, reverse-transcription polymerase chain reaction (RT-PCR), and immunocytochemistry. Results: A single major GLP-2R messenger RNA transcript was detected by Northern blot analysis in rodent stomach, duodenum, jejunum, ileum, and colon, but not in rodent esophagus, GLP-2R expression was also detected by RT-PCR in RNA from the hypothalamus, brain stem, and lung. Immunocytochemical localization of human GLP-2R expression using specific antisera detected GLP-2R immunopositivity in subsets of endocrine cell populations in the epithelium of the stomach and both the small and large bowel, Conclusions: These findings suggest that enteroendocrine-derived GLP-2 acts directly on endocrine cells to induce one or more downstream mediators of GLP-2 action in the gastrointestinal tract.