Document Detail


Prototypic G protein-coupled receptor for the intestinotrophic factor glucagon-like peptide 2.
MedLine Citation:
PMID:  9990065     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Glucagon-like peptide 2 (GLP-2) is a 33-aa proglucagon-derived peptide produced by intestinal enteroendocrine cells. GLP-2 stimulates intestinal growth and up-regulates villus height in the small intestine, concomitant with increased crypt cell proliferation and decreased enterocyte apoptosis. Moreover, GLP-2 prevents intestinal hypoplasia resulting from total parenteral nutrition. However, the mechanism underlying these actions has remained unclear. Here we report the cloning and characterization of cDNAs encoding rat and human GLP-2 receptors (GLP-2R), a G protein-coupled receptor superfamily member expressed in the gut and closely related to the glucagon and GLP-1 receptors. The human GLP-2R gene maps to chromosome 17p13.3. Cells expressing the GLP-2R responded to GLP-2, but not GLP-1 or related peptides, with increased cAMP production (EC50 = 0.58 nM) and displayed saturable high-affinity radioligand binding (Kd = 0.57 nM), which could be displaced by synthetic rat GLP-2 (Ki = 0.06 nM). GLP-2 analogs that activated GLP-2R signal transduction in vitro displayed intestinotrophic activity in vivo. These results strongly suggest that GLP-2, like glucagon and GLP-1, exerts its actions through a distinct and specific novel receptor expressed in its principal target tissue, the gastrointestinal tract.
Authors:
D G Munroe; A K Gupta; F Kooshesh; T B Vyas; G Rizkalla; H Wang; L Demchyshyn; Z J Yang; R K Kamboj; H Chen; K McCallum; M Sumner-Smith; D J Drucker; A Crivici
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  96     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1999 Feb 
Date Detail:
Created Date:  1999-03-25     Completed Date:  1999-03-25     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  1569-73     Citation Subset:  IM    
Affiliation:
Allelix Biopharmaceuticals Inc., 6850 Goreway Drive, Mississauga, Ontario L4V 1V7, Canada. dmunroe@allelix.com
Data Bank Information
Bank Name/Acc. No.:
GENBANK/AF105367;  AF105368
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Brain / metabolism
COS Cells
Cloning, Molecular
Cyclic AMP / metabolism
GTP-Binding Proteins / metabolism*
Gene Library
Glucagon-Like Peptide 1
Glucagon-Like Peptide 2
Humans
Intestines / metabolism
Kinetics
Molecular Sequence Data
Organ Specificity
Peptide Fragments / pharmacology
Peptides / pharmacology,  physiology*
Rats
Receptors, Glucagon / chemistry,  genetics,  physiology*
Sequence Alignment
Sequence Homology, Amino Acid
Signal Transduction
Structure-Activity Relationship
Transfection
Chemical
Reg. No./Substance:
0/Glucagon-Like Peptide 2; 0/Peptide Fragments; 0/Peptides; 0/Receptors, Glucagon; 0/glucagon-like peptide receptor; 60-92-4/Cyclic AMP; 89750-14-1/Glucagon-Like Peptide 1; EC 3.6.1.-/GTP-Binding Proteins
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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