The Effect of Centrally Administered CCK-Receptor Antagonists on Food Intake in Rats

A cholecystokinin monoclonal antibody (CCK MAb) was used to immunoneutralize CCK to test the hypothesis that CCK produces satiety by an endocrine mechanism. We first characterized the effects of CCK MAb on pancreatic secretion. Conscious rats with jugular vein and bile-pancreatic duct cannulas received CCK MAb or control antibody intravenously 30 min before a 2-h maximal dose of CCK-8 (200 pmol.kg-1.h-1 i.v.) or access to food. CCK MAb caused dose-related inhibition of amylase secretion. CCK MAb (2 mg/kg) completely blocked the response to CCK-8 and inhibited the response to food by 89%. In feeding experiments, rats with free access to food received CCK MAb or control antibodies (2 mg/kg iv) 2 h after lights off. CCK MAb had no effect on 1.5- or 3.5-h food intake. Another group of rats received CCK MAb (4 mg/kg i.v.) or a combined injection of type A and type B CCK receptor antagonists devazepide and L-365,260 (1 mg/kg each i.v.). CCK MAb had no effect on feeding, whereas the receptor antagonists stimulated 1-, 2-, 3-, and 4-h intake by 62, 45, 43, and 29%. These results suggest that endogenous CCK stimulates pancreatic enzyme secretion at least partially by an endocrine mechanism and produces satiety by a nonendocrine mechanism.

Download Full-text

CCK is involved in both peripheral and central mechanisms controlling food intake in chickens

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.1.r334 ◽

1997 ◽

Vol 272 (1) ◽

pp. R334-R340 ◽

Cited By ~ 6

Author(s):

A. Rodriguez-Sinovas ◽

E. Fernandez ◽

X. Manteca ◽

A. G. Fernandez ◽

E. Gonalons

Keyword(s):

Food Intake ◽

Receptor Antagonist ◽

Receptor Type ◽

Receptor Antagonists ◽

Cck Receptors ◽

High Affinity ◽

Increase Food Intake ◽

Cck Receptor Antagonist ◽

Cck Receptor Antagonists ◽

Voluntary Food Intake

The aim of this work was to study the involvement of cholecystokinin (CCK) in the control of food intake in chickens. The following aspects were studied: 1) the effects of intravenous and intracerebroventricular sulfated octapeptide of CCK (CCK-8s) on voluntary food intake; 2) the effects of two CCK-receptor antagonists. L-365,260 and L-364,718, on food intake; and 3) the ability of such drugs to block the effects of CCK-8s on food intake in the chicken. Intravenous and intracerebroventricular CCK-8s caused a decrease in food intake. Intraperitoneal L-365,260, a CCK-receptor antagonist with low affinity for the two CCK receptors described in the chicken, increases food intake. Intracerebroventricular L-364,718, a drug that has high affinity for the chicken central CCK-receptor type, increased food intake. The effect of intravenous CCK-8s on food intake was not blocked by L-364,718 or L-365,260, whereas that of intracerebroventricular CCK-8s was blocked by intracerebroventricular L-364,718. It is concluded that central endogenous CCK plays a role in the control of food intake, which is dependent on central CCK-receptor type; nevertheless, peripheral CCK also decreases food intake acting on the peripheral CCK-receptor type. The fact that intracerebroventricular L-364,718 is able to increase food intake is related to its high affinity for the central CCK-receptor type of this species. Finally, three different speculations that might explain the fact that intraperitoneal L-365,260 increases food intake are discussed.

Download Full-text

Increased food intake and CCK receptor antagonists: beyond abdominal vagal afferents

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00116.2004 ◽

2004 ◽

Vol 286 (6) ◽

pp. R991-R993 ◽

Cited By ~ 16

Author(s):

Robert C. Ritter

Keyword(s):

Food Intake ◽

Vagal Afferents ◽

Receptor Antagonists ◽

Cck Receptor Antagonists

Download Full-text

Effect of Hypothalamic Microinjection and Ventricular Perfusion of CCK Receptor Antagonists on Gut Myoelectrical Activity

Annals of the New York Academy of Sciences ◽

10.1111/j.1749-6632.1994.tb44092.x ◽

1994 ◽

Vol 713 (1 Cholecystokin) ◽

pp. 358-359 ◽

Cited By ~ 1

Author(s):

S. NITECKI ◽

G. J. HARTY ◽

J. H. SZURSZEWSKI

Keyword(s):

Receptor Antagonists ◽

Myoelectrical Activity ◽

Cck Receptor Antagonists

Download Full-text

New proglumide-analogue CCK receptor antagonists: very potent and selective for peripheral tissues

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1986.250.6.g856 ◽

1986 ◽

Vol 250 (6) ◽

pp. G856-G860 ◽

Cited By ~ 2

Author(s):

C. Niederau ◽

M. Niederau ◽

J. A. Williams ◽

J. H. Grendell

Keyword(s):

Agonist Activity ◽

Receptor Antagonists ◽

Maximal Inhibition ◽

Amylase Release ◽

Peripheral Tissues ◽

Pancreatic Acini ◽

Cholecystokinin Receptor ◽

Low Concentrations ◽

Competitive Kinetics ◽

Cck Receptor Antagonists

The present study evaluates the ability of two recently synthesized analogues of proglumide, both 4-benzamido-N,N-di-alkyl-glutaramic acid derivatives, to act as cholecystokinin receptor antagonists. Both new antagonists inhibited cholecystokinin-stimulated amylase release and, similarly, binding of 125I-cholecystokinin to isolated rat pancreatic acini. These effects displayed competitive kinetics; both antagonists showed no agonist activity and were specific in that only those secretagogues were inhibited that interact with the cholecystokinin receptor. Both antagonists also inhibited binding of 125I-cholecystokinin to mouse pancreatic membrane particles similarly to results with rat pancreatic acini. With the more potent of the two new antagonists, half-maximal inhibition of action and binding of cholecystokinin was observed with low concentrations of approximately 10(-7) M; compared with proglumide, the new antagonists were as much as 4,000 times more potent. Unlike proglumide, which inhibits binding of cholecystokinin to pancreas and brain tissue similarly, both antagonists inhibited binding of cholecystokinin to the pancreas at much lower concentrations compared with brain. The more potent of the inhibitors was 300 times more potent in inhibiting binding of cholecystokinin to pancreatic tissues compared with brain.

Download Full-text