CCK receptor antagonists possess intrinsic biologic activity that counteracts CCK agonist activity

1996 ◽  
Vol 64 (1-3) ◽  
pp. 82
Keyword(s):  
Agonist Activity ◽  
Receptor Antagonists ◽  
Biologic Activity ◽  
Cck Receptor Antagonists

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

1986 ◽  
Vol 250 (6) ◽  
pp. G856-G860 ◽  
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.

Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

1994 ◽  
Vol 267 (4) ◽  
pp. R901-R908 ◽  
Author(s):  
R. D. Reidelberger ◽  
G. Varga ◽  
R. M. Liehr ◽  
D. A. Castellanos ◽  
G. L. Rosenquist ◽  
...  
Keyword(s):  
Food Intake ◽  
Pancreatic Enzyme ◽  
Free Access ◽  
Amylase Secretion ◽  
Receptor Antagonists ◽  
Feeding Experiments ◽  
Pancreatic Enzyme Secretion ◽  
Endocrine Mechanism ◽  
Access To Food ◽  
Cck Receptor Antagonists

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.

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

1997 ◽  
Vol 61 (6) ◽  
pp. 823-827 ◽  
Author(s):  
Eric S Corp ◽  
Michael Curcio ◽  
James Gibbs ◽  
Gerard P Smith
Keyword(s):  
Food Intake ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists

Peptoid CCK receptor antagonists: pharmacological evaluation of CCKA, CCKB and mixed receptor antagonists

1995 ◽  
Vol 286 (2) ◽  
pp. 185-191 ◽  
Author(s):  
Lakhbir Singh ◽  
Mark J. Field ◽  
David R. Hill ◽  
David C. Horwell ◽  
Alexander T. McKnight ◽  
...  
Keyword(s):  
Receptor Antagonists ◽  
Pharmacological Evaluation ◽  
Cck Receptor Antagonists

Benzotriazonine as a new core structure for the design of CCK-receptor antagonists

1999 ◽  
Vol 5 (3) ◽  
pp. 155-158 ◽  
Author(s):  
Achim Escherich ◽  
Chantal Escrieut ◽  
Daniel Fourmy ◽  
Luis Moroder
Keyword(s):  
Core Structure ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists

Suppression of sham feeding by intraintestinal nutrients is not correlated with plasma cholecystokinin elevation

1993 ◽  
Vol 264 (5) ◽  
pp. R972-R976 ◽  
Author(s):  
L. Brenner ◽  
D. P. Yox ◽  
R. C. Ritter
Keyword(s):  
Sucrose Solution ◽  
Elevated Plasma ◽  
Receptor Antagonists ◽  
Sham Feeding ◽  
Plasma Cholecystokinin ◽  
Intestinal Infusion ◽  
Cck Receptor Antagonists ◽  
Elevate Plasma ◽  
Nutrient Infusion

To test the possibility that blood-borne cholecystokinin (CCK) participates in suppression of sham feeding by intestinal nutrients in rats, we examined the ability of oleate, maltose, L-phenylalanine (L-Phe), and casein to suppress sham ingestion of 15% sucrose solution. Plasma CCK concentrations were measured in parallel experiments in which the same intestinal nutrients were infused in rats that were not feeding. Intraintestinal oleate suppressed sham feeding and elevated plasma CCK concentrations. Casein infusion produced plasma CCK concentrations similar to those produced by oleate but did not suppress sham feeding. Both maltose and L-Phe suppressed sham feeding but failed to significantly elevate plasma CCK. Previously we demonstrated that CCK receptor antagonists attenuate suppression of sham feeding by intestinal infusion of either oleate or maltose, suggesting that endogenous CCK participates in suppression of sham feeding by some intestinal nutrients. The results of the study reported here suggest that plasma CCK levels after nutrient infusion are not correlated with suppression of sham feeding. Therefore, the mechanism of CCK's participation in nutrient-induced suppression of sham feeding may not depend on stimulus-induced elevation of plasma CCK.

CCK-receptor antagonists proglumide and loxiglumide stimulate bile flow and biliary glutathione excretion

1994 ◽  
Vol 39 (9) ◽  
pp. 1974-1980 ◽  
Author(s):  
Krystyna Sztefko ◽  
Ping Li ◽  
Nazzareno Ballatori ◽  
William Y. Chey
Keyword(s):  
Bile Flow ◽  
Receptor Antagonists ◽  
Cck Receptor Antagonists
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