| 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 |
Related Documents
:
|
18442383 - Regulation of osmoadaptation in the moderate halophile halobacillus halophilus: chlorid... 11485823 - Resveratrol and quercetin inhibit angiogenesis in vitro. 17850673 - Distance to food stores & adolescent male fruit and vegetable consumption: mediation ef... |
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 |
Export Citation:
|
APA/MLA Format Download EndNote Download BibTex |
| 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
Previous Document: The heme oxygenase-1 pathway is involved in calcitonin gene-related peptide-mediated delayed cardiop...
Next Document: Angiotensin-(1-7) reverts the stimulatory effect of angiotensin II on the proximal tubule Na(+)-ATPa...