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 up-regulates 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.

[1]  P. Yang,et al.  Glucagon-like peptide-2 enhances intestinal epithelial barrier function of both transcellular and paracellular pathways in the mouse , 2000, Gut.

[2]  M. Schwartz,et al.  Glucagonlike peptide-2 analogue enhances intestinal mucosal mass after ischemia and reperfusion. , 2000, Journal of pediatric surgery.

[3]  J. Habener,et al.  The glucagon-like peptides. , 1999, Endocrine reviews.

[4]  B. Yusta,et al.  Glucagon-like peptide 2 decreases mortality and reduces the severity of indomethacin-induced murine enteritis. , 1999, The American journal of physiology.

[5]  S. Grinstein,et al.  Identification of Glucagon-like Peptide-2 (GLP-2)-activated Signaling Pathways in Baby Hamster Kidney Fibroblasts Expressing the Rat GLP-2 Receptor* , 1999, The Journal of Biological Chemistry.

[6]  T. Usdin,et al.  Distribution of the Parathyroid Hormone 2 Receptor in Rat: Immunolocalization Reveals Expression by Several Endocrine Cells. , 1999, Endocrinology.

[7]  B. Hartmann,et al.  Inhibition of sham feeding-stimulated human gastric acid secretion by glucagon-like peptide-2. , 1999, The Journal of clinical endocrinology and metabolism.

[8]  D. Drucker.  Glucagon-like Peptide 2 , 1999, Trends in Endocrinology & Metabolism.

[9]  D. Drucker,et al.  Identification of Domains Mediating Transcriptional Activation and Cytoplasmic Export in the Caudal Homeobox Protein Cdx-3* , 1999, The Journal of Biological Chemistry.

[10]  D. Drucker,et al.  Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[11]  B. Yusta,et al.  Human [Gly2]GLP-2 reduces the severity of colonic injury in a murine model of experimental colitis. , 1999, The American journal of physiology.

[12]  B. Göke,et al.  Biological actions of glucagon-like peptide(GLP)-2 revealed--how pluripotential is the glucagon gene? , 2009, Experimental and clinical endocrinology & diabetes : official journal, German Society of Endocrinology [and] German Diabetes Association.

[13]  W. MacNaughton,et al.  GLP-2 augments the adaptive response to massive intestinal resection in rat , 1998 .

[14]  A. Buchan,et al.  Glucagon-like-peptide-1 secretion from canine L-cells is increased by glucose-dependent-insulinotropic peptide but unaffected by glucose. , 1998, Endocrinology.

[15]  D. Drucker.  Glucagon-Like Peptides , 1998, Diabetes.

[16]  J. Holst,et al.  Glucagon-like peptide-2 inhibits centrally induced antral motility in pigs. , 1998, Scandinavian journal of gastroenterology.

[17]  M. Jackerott,et al.  Immunocytochemical Localization of the NPY/PYY Y1 Receptor in Enteric Neurons, Endothelial Cells, and Endocrine-like Cells of the Rat Intestinal Tract , 1997, Journal of Histochemistry and Cytochemistry.

[18]  C. Sternini,et al.  Somatostatin 2A receptor is expressed by enteric neurons, and by interstitial cells of Cajal and enterochromaffin‐like cells of the gastrointestinal tract , 1997, The Journal of comparative neurology.

[19]  W. Chance,et al.  Prevention of parenteral nutrition-induced gut hypoplasia by coinfusion of glucagon-like peptide-2. , 1997, The American journal of physiology.

[20]  D. Drucker,et al.  Regulation of the biological activity of glucagon-like peptide 2 in vivo by dipeptidyl peptidase IV , 1997, Nature Biotechnology.

[21]  添田仁一.  Mucosal Neuroendocrine Cell Abnormalities in the Colon of Patients With Hirschsprung′s Disease(ヒルシュスプルング病の大腸における粘膜神経分泌細胞の異常) , 1997 .

[22]  D. Drucker,et al.  Induction of intestinal epithelial proliferation by glucagon-like peptide 2. , 1996, Proceedings of the National Academy of Sciences of the United States of America.

[23]  J. Habener,et al.  Tissue distribution of messenger ribonucleic acid encoding the rat glucagon-like peptide-1 receptor. , 1996, Endocrinology.

[24]  P. Brubaker,et al.  Gastrin-releasing peptide is a novel mediator of proximal nutrient-induced proglucagon-derived peptide secretion from the distal gut. , 1996, Endocrinology.

[25]  J. Brown,et al.  Functional expression of the rat pancreatic islet glucose-dependent insulinotropic polypeptide receptor: ligand binding and intracellular signaling properties. , 1995, Endocrinology.

[26]  S. Iseki,et al.  The occurrence of acidic fibroblast growth factor-like immunoreactivity in subpopulations of endocrine cells in the pancreas and intestine of the rat. , 1995, Archives of histology and cytology.

[27]  B. Göke,et al.  Molecular cloning of a cDNA encoding for the GLP-1 receptor expressed in rat lung. , 2009, Experimental and clinical endocrinology.

[28]  D. Drucker,et al.  Activation of proglucagon gene transcription by protein kinase-A in a novel mouse enteroendocrine cell line. , 1994, Molecular endocrinology.

[29]  D. Drucker,et al.  Divergent tissue-specific and developmental expression of receptors for glucagon and glucagon-like peptide-1 in the mouse. , 1994, Endocrinology.

[30]  P. Fuller,et al.  7 Humoral regulation of intestinal adaptation , 1994 .

[31]  R. Taylor,et al.  Humoral regulation of intestinal adaptation. , 1994, Bailliere's clinical endocrinology and metabolism.

[32]  P. Brubaker,et al.  Regulation of intestinal proglucagon-derived peptide secretion by glucose-dependent insulinotropic peptide in a novel enteroendocrine loop. , 1993, Endocrinology.

[33]  F J Grant,et al.  Expression cloning and signaling properties of the rat glucagon receptor. , 1993, Science.

[34]  D. Drucker,et al.  Multiple cis-acting domains mediate basal and adenosine 3',5'-monophosphate-dependent glucagon gene transcription in a mouse neuroendocrine cell line. , 1993, Endocrinology.

[35]  D. Podolsky.  Regulation of intestinal epithelial proliferation: a few answers, many questions. , 1993, The American journal of physiology.

[36]  B. Thorens.  Expression cloning of the pancreatic beta cell receptor for the gluco-incretin hormone glucagon-like peptide 1. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[37]  G. Stamp,et al.  Trefoil peptide expression in intestinal adaptation and renewal. , 1992, Scandinavian journal of gastroenterology. Supplement.

[38]  John R. Christiansen,et al.  Oxyntomodulin: a potential hormone from the distal gut. Pharmacokinetics and effects on gastric acid and insulin secretion in man , 1988, European journal of clinical investigation.

[39]  S. Asa,et al.  Pancreatic endocrine tumour producing growth hormone-releasing hormone associated with multiple endocrine neoplasia type I syndrome. , 1987, Acta endocrinologica.

[40]  P. Chomczyński,et al.  Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. , 1987, Analytical biochemistry.

[41]  C. Dani,et al.  Post-transcriptional regulation of glyceraldehyde-3-phosphate-dehydrogenase gene expression in rat tissues. , 1984, Nucleic acids research.

[42]  F. Sundler,et al.  Enteropathy ofcoeliac disease inadults: increased numberofenterochromaffin cells inthe duodenal mucosa , 1982 .

[43]  F. Sundler,et al.  Duodenal endocrine cells in adult coeliac disease. , 1979, Gut.