Document Detail


Lack of tolerance development with long-term administration of PEGylated cholecystokinin.
MedLine Citation:
PMID:  19084041     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
Isabelle Verbaeys; Fabián León-Tamariz; Johan Buyse; Eddy Decuypere; Hans Pottel; Marnix Cokelaere
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2008-11-25
Journal Detail:
Title:  Peptides     Volume:  30     ISSN:  1873-5169     ISO Abbreviation:  Peptides     Publication Date:  2009 Apr 
Date Detail:
Created Date:  2009-03-30     Completed Date:  2009-08-05     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8008690     Medline TA:  Peptides     Country:  United States    
Other Details:
Languages:  eng     Pagination:  699-704     Citation Subset:  IM    
Affiliation:
Interdisciplinary Research Center, Katholieke Universiteit Leuven, Campus Kortrijk, Belgium. isabelle.verbaeys@kuleuven-kortrijk.be
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MeSH Terms
Descriptor/Qualifier:
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:
0/Polyethylene Glycols; 9011-97-6/Cholecystokinin

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


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