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

Background & Aims: Glucagon-like peptide (GLP)-2, a product of the progluca gon gene, is expressed in enteroendocrine cells of the small and large inte stine and is trophic to the gastrointestinal mucosa. GLP-2 also inhibits ga stric acid secretion and emptying and upregulates intestinal hexose transpo rt. GLP-2 acts via binding to a single G protein-coupled GLP-2 receptor (GL P-2R), but the cellular targets for the diverse actions of GLP-2 remain unk nown. Methods: GLP-2R expression in rodent and human tissues was examined u sing a combination of Northern blotting, reverse-transcription polymerase c hain reaction (RT-PCR), and immunocytochemistry. Results: A single major GL P-2R messenger RNA transcript was detected by Northern blot analysis in rod ent stomach, duodenum, jejunum, ileum, and colon, but not in rodent esophag us, GLP-2R expression was also detected by RT-PCR in RNA from the hypothala mus, brain stem, and lung. Immunocytochemical localization of human GLP-2R expression using specific antisera detected GLP-2R immunopositivity in subs ets of endocrine cell populations in the epithelium of the stomach and both the small and large bowel, Conclusions: These findings suggest that entero endocrine-derived GLP-2 acts directly on endocrine cells to induce one or m ore downstream mediators of GLP-2 action in the gastrointestinal tract.