Lack of tolerance development with long-term administration of PEGylated cholecystokinin. 2009

Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
Interdisciplinary Research Center, Katholieke Universiteit Leuven, Campus Kortrijk, Belgium. isabelle.verbaeys@kuleuven-kortrijk.be

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.

UI MeSH Term Description Entries
D007274 Injections, Intraperitoneal Forceful administration into the peritoneal cavity of liquid medication, nutrient, or other fluid through a hollow needle piercing the abdominal wall. Intraperitoneal Injections,Injection, Intraperitoneal,Intraperitoneal Injection
D007677 Kidney Function Tests Laboratory tests used to evaluate how well the kidneys are working through examination of blood and urine. Function Test, Kidney,Function Tests, Kidney,Kidney Function Test,Test, Kidney Function,Tests, Kidney Function
D008111 Liver Function Tests Blood tests that are used to evaluate how well a patient's liver is working and also to help diagnose liver conditions. Function Test, Liver,Function Tests, Liver,Liver Function Test,Test, Liver Function,Tests, Liver Function
D008297 Male Males
D010179 Pancreas A nodular organ in the ABDOMEN that contains a mixture of ENDOCRINE GLANDS and EXOCRINE GLANDS. The small endocrine portion consists of the ISLETS OF LANGERHANS secreting a number of hormones into the blood stream. The large exocrine portion (EXOCRINE PANCREAS) is a compound acinar gland that secretes several digestive enzymes into the pancreatic ductal system that empties into the DUODENUM.
D011092 Polyethylene Glycols Polymers of ETHYLENE OXIDE and water, and their ethers. They vary in consistency from liquid to solid depending on the molecular weight indicated by a number following the name. They are used as SURFACTANTS, dispersing agents, solvents, ointment and suppository bases, vehicles, and tablet excipients. Some specific groups are NONOXYNOLS, OCTOXYNOLS, and POLOXAMERS. Macrogols,Polyoxyethylenes,Carbowax,Macrogol,Polyethylene Glycol,Polyethylene Oxide,Polyethyleneoxide,Polyglycol,Glycol, Polyethylene,Glycols, Polyethylene,Oxide, Polyethylene,Oxides, Polyethylene,Polyethylene Oxides,Polyethyleneoxides,Polyglycols,Polyoxyethylene
D001835 Body Weight The mass or quantity of heaviness of an individual. It is expressed by units of pounds or kilograms. Body Weights,Weight, Body,Weights, Body
D002766 Cholecystokinin A peptide, of about 33 amino acids, secreted by the upper INTESTINAL MUCOSA and also found in the central nervous system. It causes gallbladder contraction, release of pancreatic exocrine (or digestive) enzymes, and affects other gastrointestinal functions. Cholecystokinin may be the mediator of satiety. Pancreozymin,CCK-33,Cholecystokinin 33,Uropancreozymin
D004361 Drug Tolerance Progressive diminution of the susceptibility of a human or animal to the effects of a drug, resulting from its continued administration. It should be differentiated from DRUG RESISTANCE wherein an organism, disease, or tissue fails to respond to the intended effectiveness of a chemical or drug. It should also be differentiated from MAXIMUM TOLERATED DOSE and NO-OBSERVED-ADVERSE-EFFECT LEVEL. Drug Tolerances,Tolerance, Drug,Tolerances, Drug
D005247 Feeding Behavior Behavioral responses or sequences associated with eating including modes of feeding, rhythmic patterns of eating, and time intervals. Dietary Habits,Eating Behavior,Faith-based Dietary Restrictions,Feeding Patterns,Feeding-Related Behavior,Food Habits,Diet Habits,Eating Habits,Behavior, Eating,Behavior, Feeding,Behavior, Feeding-Related,Behaviors, Eating,Behaviors, Feeding,Behaviors, Feeding-Related,Diet Habit,Dietary Habit,Dietary Restriction, Faith-based,Dietary Restrictions, Faith-based,Eating Behaviors,Eating Habit,Faith based Dietary Restrictions,Faith-based Dietary Restriction,Feeding Behaviors,Feeding Pattern,Feeding Related Behavior,Feeding-Related Behaviors,Food Habit,Habit, Diet,Habit, Dietary,Habit, Eating,Habit, Food,Habits, Diet,Pattern, Feeding,Patterns, Feeding,Restrictions, Faith-based Dietary

Related Publications

Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1990, Cardiology,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1977, Science (New York, N.Y.),
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1989, Progress in clinical and biological research,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
November 1991, Pain,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
May 1989, Connecticut medicine,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1989, Zeitschrift fur Kardiologie,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1989, European journal of clinical pharmacology,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
April 1957, Annals of the New York Academy of Sciences,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
January 1986, Psychopharmacology bulletin,
Isabelle Verbaeys, and Fabián León-Tamariz, and Johan Buyse, and Eddy Decuypere, and Hans Pottel, and Marnix Cokelaere
July 1988, Cardiovascular drugs and therapy,
Copied contents to your clipboard!