| Lack of tolerance development with long-term administration of PEGylated cholecystokinin. | |
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MedLine Citation:
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PMID: 19084041 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Cholecystokinin (CCK) is a short acting satiating peptide hormone produced in the proximal small intestine. Daily CCK injection in rats initially inhibits food intake, but after several days, food intake is no longer affected, suggesting development of tolerance. Previously, we covalently coupled CCK to a 10kDa polyethylene glycol (mPEG-OH) and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9). The present study examined whether tolerance to the anorectic effect develops during long-term administration of PEG-CCK(9). For 14 consecutive days, male Wistar rats (n=12) received a daily i.p injection of 8microgkg(-1) of PEG-CCK(9) and a control group received a daily control injection of mPEG-OH. Body weight and food intake were monitored daily during the experiment. Effects on the pancreas were investigated. On each day, injection of PEG-CCK(9) induced an anorectic effect lasting 3-6h, but failed to significantly reduce daily total food intake compared to controls. The body weight gain of the PEG-CCK(9)-treated animals was not different from controls. The PEG-CCK(9)-treated group had a significantly higher pancreas weight, mainly due to hyperplasia. In conclusion, PEG-CCK(9) continued to have a daily suppressive effect on food intake when administered for 14 consecutive days, showing there was no development of tolerance. |
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Authors:
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Isabelle Verbaeys; Fabián León-Tamariz; Johan Buyse; Eddy Decuypere; Hans Pottel; Marnix Cokelaere |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2008-11-25 |
Journal Detail:
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Title: Peptides Volume: 30 ISSN: 1873-5169 ISO Abbreviation: Peptides Publication Date: 2009 Apr |
Date Detail:
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Created Date: 2009-03-30 Completed Date: 2009-08-05 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8008690 Medline TA: Peptides Country: United States |
Other Details:
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Languages: eng Pagination: 699-704 Citation Subset: IM |
Affiliation:
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Interdisciplinary Research Center, Katholieke Universiteit Leuven, Campus Kortrijk, Belgium. isabelle.verbaeys@kuleuven-kortrijk.be |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Body Weight / drug effects Cholecystokinin / administration & dosage*, chemistry, pharmacology Drug Tolerance Feeding Behavior / drug effects Injections, Intraperitoneal Kidney Function Tests Liver Function Tests Male Pancreas / chemistry Polyethylene Glycols / chemistry* Rats Rats, Wistar |
| Chemical | |
Reg. No./Substance:
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0/Polyethylene Glycols; 9011-97-6/Cholecystokinin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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