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Title: PEGylated cholecystokinin prolongs satiation in rats: dose dependency and receptor involvement
Authors: Verbaeys, Isabelle ×
León-Tamariz, F
Buyse, Johan
De Cuyper, Marcel
Pottel, Hans
Van Boven, Maurits
Cokelaere, Marnix #
Issue Date: Oct-2007
Publisher: Scientific & Medical Division, Macmillan Press
Series Title: British Journal of Pharmacology vol:152 issue:3 pages:396-403
Abstract: Background and purpose:Acute intraperitoneal (i.p.) administration of cholecystokinin (CCK) is known to induce a significant, but short-lasting, reduction in food intake, followed by recovery within hours. Therefore, we had covalently coupled CCK to a 10 kDa polyethylene glycol and showed that this conjugate, PEG-CCK(9), produced a significantly longer anorectic effect than unmodified CCK(9). The present study assessed the dose-dependency of this response and the effect of two selective CCK(1) receptor antagonists, with different abilities to cross the blood-brain barrier (BBB), on PEG-CCK(9)-induced anorexia.Experimental approach:Food intake was measured, for up to 23 h, after i.p. administration of different doses (2, 4, 8, 16 and 32 mug kg(-1)) of CCK(9) or PEG-CCK(9) in male Wistar rats. Devazepide (100 mug kg(-1)), which penetrates the BBB or 2-NAP (3 mg kg(-1)), which does not cross the BBB, were coadministered i.p. with PEG-CCK(9) (6 mug kg(-1)) and food intake was monitored.Key results:In PEG-CCK(9)-treated rats, a clear dose-dependency was seen for both the duration and initial intensity of the anorexia whereas, for CCK(9), only the initial intensity was dose-dependent. Intraperitoneal administration of devazepide or 2-NAP, injected immediately prior to PEG-CCK(9), completely abolished the anorectic effect of PEG-CCK(9).Conclusions and implications:The duration of the anorexia for PEG-CCK(9) was dose-dependent, suggesting that PEGylation of CCK(9) increases its circulation time. Both devazepide and 2-NAP completely abolished the anorectic effect of i.p. PEG-CCK(9) indicating that its anorectic effect was solely due to stimulation of peripheral CCK(1) receptors.British Journal of Pharmacology advance online publication, 9 July 2007; doi:10.1038/sj.bjp.0707390.
URI: 
ISSN: 0007-1188
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Interdisciplinary Research Facility Life Sciences, Campus Kulak Kortrijk
Anatomy, Kulak (-)
Division of Livestock-Nutrition-Quality (-)
Faculty of Medicine, Campus Kulak Kortrijk
Toxicology and Pharmacology
× corresponding author
# (joint) last author

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