Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

Reidelberger, Roger D.; Varga, Gábor; Liehr, Ralf-Marco; Castellanos, Daniel A.; Rosenquist, Grace L.; Wong, Hoi Man; Walsh, John H.

doi:10.1152/ajpregu.1994.267.4.r901

Cited by 31 publications

(23 citation statements)

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“…For example, a CCK monoclonal antibody that completely blocks the response to CCK-8, the active hormone, in rats had no effect on their feeding responses to a meal (5). A paracrine mode of action is also consistent with morphological studies showing that close proximity exists between vagal afferent fibers and the basolateral membranes of CCK immunoreactive epithelial cells (6).…”

Section: Cholecystokinin (Cck)supporting

confidence: 69%

Cholecystokinin-A Receptors Are Involved in Food Intake Suppression in Rats after Intake of all Fats and Carbohydrates Tested

Bellissimo

Anderson

2003

The Journal of Nutrition

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The hypothesis of these studies was that all fats and carbohydrates suppress food intake, at least in part, via cholecystokinin-A receptors (CCKAR). Fat (coconut oil, beef tallow, olive and safflower oil) and carbohydrate (cornstarch, sucrose, glucose and fructose) preloads were given intragastrically (1 g/4 mL) 30 min before feeding. Devazepide (0.25 mg/kg), a CCKAR antagonist, was given intraperitoneally at 60 or 30 min before or with each of the macronutrient preloads. Devazepide reversed food intake suppression caused by all fat and carbohydrate sources, but the effect was not consistently related to the time of devazepide administration or to any specific feeding interval. Among the fats, coconut and olive oil were most responsive to devazepide. The effect of all carbohydrates on food intake was decreased by devazepide. We conclude that CCKAR play a role in food intake suppression caused by all fats and carbohydrates, but their role is dependent upon the composition of the fat or carbohydrate.

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Section: Cholecystokinin (Cck)supporting

confidence: 69%

Cholecystokinin-A Receptors Are Involved in Food Intake Suppression in Rats after Intake of all Fats and Carbohydrates Tested

Bellissimo

Anderson

2003

The Journal of Nutrition

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“…The present study demonstrated that duodenal infusions of maltose, peptone, and Intralipid dose dependently inhibited sham feeding, and inhibitory responses to each macronutrient were attenuated by both A-70104 and devazepide. We previously determined that in rats, immunoneutralization of circulating CCK blocks nutrient-induced stimulation of pancreatic enzyme secretion but has no effect on food intake (50). Together, these results suggest that endogenous CCK acts by an essential paracrine and/or neurocrine mechanism at CCKARs peripheral to the bloodbrain barrier to inhibit food intake.…”

Section: Discussionmentioning

confidence: 96%

Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats

Reidelberger

Heimann

Kelsey

et al. 2003

American Journal of Physiology-Regulatory, Integrative and Comp

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A cholecystokinin receptor (CCKAR) antagonists differing in blood-brain barrier permeability were used to test the hypothesis that duodenal delivery of protein, carbohydrate, and fat produces satiety in part by an essential CCK action at CCKARs located peripheral to the blood-brain barrier. Fasted rats with open gastric fistulas received devazepide (1 mg/kg iv) or A-70104 (700 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 iv) and either a 30-min intravenous infusion of CCK-8 (10 nmol ⅐ kg Ϫ1 ⅐ h Ϫ1 ) or duodenal infusion of peptone, maltose, or Intralipid beginning 10 min before 30-min access to 15% sucrose. Devazepide penetrates the blood-brain barrier; A-70104, the dicyclohexylammonium salt of N␣-3-quinolinoyl-D-Glu-N,N-dipentylamide, does not. CCK-8 inhibited sham feeding by ϳ50%, and both A-70104 and devazepide abolished this response. Duodenal infusion of each of the macronutrients dose dependently inhibited sham feeding. A-70104 and devazepide attenuated inhibitory responses to each macronutrient. Thus endogenous CCK appears to act in part at CCKARs peripheral to the blood-brain barrier to inhibit food intake. receptor antagonist; devazepide; A-70104; satiety CCK is a peptide that is found throughout the brain and in neurons and endocrine cells of the gastrointestinal tract. Studies demonstrating that type A CCK receptor (CCKAR) antagonists stimulate food intake in a variety of species provide compelling evidence that CCK plays an essential role in producing the satiation that occurs with ingestion of a meal (6,13,14,23,39,48). The popular hypothesis is that CCK, secreted from enteroendocrine cells in the upper small intestine in response to duodenal delivery of nutrients, acts through paracrine stimulation of intestinal vagal sensory neurons to inhibit food intake. This hypothesis is supported by studies demonstrating the existence of CCK-secreting endocrine cells in the epithelium of the upper small intestine (7, 60), CCKARs within vagal afferent nerves (40, 66), activation of intestinal vagal afferent neurons by exogenous and endogenous CCK (17,20,31), and similar attenuation by CCKAR antagonists and vagal neural lesions of anorexic responses to exogenous CCK and nutrient administration (51).Several lines of evidence suggest that this mechanism is not the only one by which CCK produces satiety. For example, we and others have demonstrated that systemic administration of the CCKAR antagonist devazepide can increase food intake in rats whether or not they are vagotomized (45) or pretreated with capsaicin to lesion visceral sensory nerves (52). CCKAR antagonists reported not to cross the bloodbrain barrier [2-naphthalenesulfonyl-L-aspartyl-2-(phenethyl)-amide (25) and A-70104 (64)] have also been reported to have no effect on food intake in rats (22) or pigs (4, 24) when administered systemically under the same conditions in which devazepide stimulates food intake (22, 23). Because CCK does not readily penetrate the blood-brain barrier (41), these results suggest that endogenous CCK may also be acting as a neurotransmitter or neuro...

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“…54,55 CCK delays gastric emptying, 56 stimulates gallbladder contraction, 57,58 results in the release of pancreatic enzymes, 59,60 and suppresses food intake. 56,59 …”

Section: Discussionmentioning

confidence: 99%

Changes in duodenal enteroendocrine cells in patients with irritable bowel syndrome following dietary guidance

Mazzawi

2017

Exp Biol Med (Maywood)

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Several contributing factors to the symptomology of irritable bowel syndrome (IBS) have been identified, such as abnormal densities of enteroendocrine cells and diet; however, the interactions between these factors have not been studied yet. The current study aims at exploring the dynamic changes between these two factors by studying the effect of using low fermentable oligo-, di-, monosaccharides and polyol (FODMAP) diet (known to improve IBS symptoms) through dietary guidance on the enteroendocrine cell densities in the duodenum. The findings showed that the densities of different enteroendocrine cells in the duodenum were abnormal before the patients received dietary guidance and tend to change/normalize after receiving guidance, which may have contributed in improving the symptoms of IBS. These findings highlight the importance of enteroendocrine cells in IBS pathophysiology and the mechanism behind the positive effect of low FODMAP dietary guidance in improving IBS symptoms and its usage as first step in the line of IBS management. AbstractThe densities of enteroendocrine cells are abnormal in patients with irritable bowel syndrome (IBS); however, they tend to change toward normal levels in stomach, ileum, and colon following dietary guidance. The aim was to identify the types of duodenal enteroendocrine cells affected after receiving dietary guidance in the same group of patients with IBS. Fourteen patients with IBS and 14 control subjects were included. The patients received three sessions of dietary guidance. Both groups underwent gastroscopies at baseline, and again for the patients after 3-9 months (median, four months) from receiving dietary guidance. Tissue biopsies were collected from the descending part of the duodenum and were immunostained for all the types of enteroendocrine cells and were then quantified by using computerized image analysis. Using the Kruskal-Wallis non-parametric test with Dunn's test as a post-test, the results showed a significant difference in the secretin cell densities between control subjects and patients with IBS prior to and following dietary guidance (P ¼ 0.0001 and 0.011, respectively). The corresponding P values for cholecystokinin (CCK) cell densities were 0.03 and 0.42, respectively; gastric inhibitory peptide (GIP) cell densities were 0.06 and 0.43, respectively; serotonin cell densities were <0.0001 and 0.002, respectively; and for somatostatin cell densities were <0.0001 and 0.052, respectively. The Paired t-test showed a significant difference only in the serotonin (P ¼ 0.03) and somatostatin (P < 0.0001) cell densities between IBS patients prior to and following dietary guidance. The changes in the cell densities of secretin, CCK, and GIP were not significant between IBS patients prior to and following dietary guidance. In conclusion, the densities of several duodenal enteroendocrine cells in IBS patients changed toward the values measured in control subjects following dietary guidance. The changes in serotonin and somatostatin cell densities may have contrib...

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Cholecystokinin suppresses food intake by a nonendocrine mechanism in rats

Cited by 31 publications

References 0 publications

Cholecystokinin-A Receptors Are Involved in Food Intake Suppression in Rats after Intake of all Fats and Carbohydrates Tested

Cholecystokinin-A Receptors Are Involved in Food Intake Suppression in Rats after Intake of all Fats and Carbohydrates Tested

Effects of peripheral CCK receptor blockade on feeding responses to duodenal nutrient infusions in rats

Changes in duodenal enteroendocrine cells in patients with irritable bowel syndrome following dietary guidance

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