Document Detail


The truncated metabolite GLP-2 (3-33) interacts with the GLP-2 receptor as a partial agonist.
MedLine Citation:
PMID:  11738243     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The therapeutic potential of the intestinotrophic mediator glucagon-like peptide-2 (1-33) [GLP-2 (1-33)] has increased interest in the pharmacokinetics of the peptide. This study was undertaken to investigate whether the primary degradation product GLP-2 (3-33) interacts with the GLP-2 receptor. Functional (cAMP) and binding in vitro studies were carried out in cells expressing the transfected human GLP-2 receptor. Furthermore, a biologic response of GLP-2 (3-33) was tested in vivo. Mice were allocated to groups treated for 10 days (twice daily) with: (1) 5 microg GLP-2 (1-33), (2) 25 microg GLP-2 (3-33), (3) 5 microg GLP-2 (1-33)+100 microg GLP-2 (3-33), or (4) 5 microg GLP-2 (1-33)+500 microg GLP-2 (3-33). The intestine was investigated for growth changes. GLP-2 (3-33) bound to the GLP-2 receptor with a binding affinity of 7.5% of that of GLP-2 (1-33). cAMP accumulation was stimulated with an efficacy of 15% and a potency more than two orders of magnitude lower than that of GLP-2 (1-33). Increasing doses of GLP-2 (3-33) (10(-7)-10(-5) M) caused a shift to the right in the dose-response curve of GLP-2 (1-33). Treatment of mice with either GLP-2 (1-33) or (3-33) induced significant growth responses in both the small and large intestines, but the response induced by GLP-2 (3-33) was much smaller. Co-administration of 500 microg of GLP-2 (3-33) and 5 microg GLP-2 (1-33) resulted in a growth response that was smaller than that of 5 microg GLP-2 (1-33) alone. Consistent with the observed in vivo activities, our functional studies and binding data indicate that GLP-2 (3-33) acts as a partial agonist with potential competitive antagonistic properties on the GLP-2 receptor.
Authors:
Jesper Thulesen; Lotte Bjerre Knudsen; Bolette Hartmann; Sven Hastrup; Hannelouise Kissow; Palle Bekker Jeppesen; Cathrine Ørskov; Jens Juul Holst; Steen Seier Poulsen
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Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Regulatory peptides     Volume:  103     ISSN:  0167-0115     ISO Abbreviation:  Regul. Pept.     Publication Date:  2002 Jan 
Date Detail:
Created Date:  2001-12-13     Completed Date:  2002-04-16     Revised Date:  2013-03-19    
Medline Journal Info:
Nlm Unique ID:  8100479     Medline TA:  Regul Pept     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  9-15     Citation Subset:  IM    
Affiliation:
Department of Medical Anatomy, Section B, The Panum Institute, University of Copenhagen, Blegdamsvej 3, 2200 N, Copenhagen, Denmark. J.Thulesen@mai.ku.dk
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight
Cell Line
Cricetinae
Cyclic AMP / metabolism
Drug Administration Schedule
Female
Glucagon-Like Peptide 2
Glucagon-Like Peptides
Humans
Image Processing, Computer-Assisted
Injections, Subcutaneous
Intestine, Large / cytology,  drug effects,  growth & development*
Intestine, Small / cytology,  drug effects,  growth & development*
Mice
Mice, Inbred C57BL
Organ Size / drug effects
Peptide Fragments / chemistry,  pharmacology*
Protein Binding
Random Allocation
Receptors, Glucagon / agonists*,  metabolism
Recombinant Proteins / administration & dosage,  metabolism
Transfection
Chemical
Reg. No./Substance:
0/Glucagon-Like Peptide 2; 0/Peptide Fragments; 0/Receptors, Glucagon; 0/Recombinant Proteins; 0/glucagon-like peptide-1 receptor; 0/glucagon-like peptide-2 (3-33); 60-92-4/Cyclic AMP; 62340-29-8/Glucagon-Like Peptides

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


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