CCK-8 decreases food intake and gastric emptying after pylorectomy or pyloroplasty

1988 ◽  
Vol 255 (1) ◽  
pp. R113-R116
Author(s):  
G. P. Smith ◽  
J. Falasco ◽  
T. H. Moran ◽  
K. M. Joyner ◽  
J. Gibbs
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Binding Sites ◽  
Specific Binding ◽  
Circular Muscle ◽  
Pyloric Sphincter ◽  
Inhibitory Effects ◽  
Cck Receptors ◽  
Adult Rat ◽  
Pyloric Muscle

Specific binding sites for cholecystokinin (CCK) in the gastrointestinal tract of the adult rat are limited to the gastroduodenal region and are concentrated in the circular muscle of the pyloric sphincter. To determine the relationship of these pyloric muscle binding sites to the inhibition by CCK of food intake and of gastric emptying, these inhibitory effects of CCK were investigated in rats that had the pyloric sphincter surgically removed or that had the pyloric sphincter contractile mechanism damaged by a pyloroplasty procedure. CCK-8 decreased food intake and gastric emptying significantly in rats after pylorectomy or pyloroplasty. This demonstrates that an intact pyloric sphincter is not necessary for these inhibitory effects in rats. Because we found autoradiographic evidence for CCK receptors near the gastroduodenal anastomosis, however, the results suggest either that these receptors mediated the inhibition of food intake and emptying by CCK-8 or that these effects depend on CCK receptors in other locations.

Effects of pylorectomy on cholecystokinin-induced inhibition of liquid gastric emptying

1991 ◽  
Vol 261 (3) ◽  
pp. R531-R535 ◽  
Author(s):  
T. H. Moran ◽  
R. J. Crosby ◽  
P. R. McHugh
Keyword(s):  
Gastric Emptying ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Pyloric Sphincter ◽  
Surgical Removal ◽  
Cck Receptors ◽  
Circular Muscle Layer ◽  
Before And After ◽  
Saline Test

The present study was designed to investigate a role for the pyloric sphincter and its population of cholecystokinin (CCK) receptors localized to the circular muscle layer in the inhibition of gastric emptying produced by exogenously administered CCK in rats. We examined the ability of two doses of CCK to inhibit the gastric emptying of 10-ml saline (0.9% NaCl) and glucose (0.125 g/ml) test meals in rats equipped with chronic gastric fistulas before and after surgical removal of the region of the pylorus containing CCK receptors. Preoperatively, CCK (2 and 8 micrograms/kg) inhibited gastric emptying of both saline and glucose. Pylorectomy did not significantly alter the baseline saline and glucose emptying and did not alter the ability of CCK to inhibit the emptying of the saline test meals. In contrast, pylorectomy eliminated the ability of CCK to inhibit glucose emptying. These results demonstrate that the inhibition of gastric emptying by CCK may involve multiple mechanisms depending on the character of the gastrointestinal contents.

Pylorectomy reduces the satiety action of cholecystokinin

1988 ◽  
Vol 255 (6) ◽  
pp. R1059-R1063 ◽  
Author(s):  
T. H. Moran ◽  
L. Shnayder ◽  
A. M. Hostetler ◽  
P. R. McHugh
Keyword(s):  
Binding Sites ◽  
Contractile Response ◽  
Behavioral Responses ◽  
Circular Muscle ◽  
Muscle Layer ◽  
Pyloric Sphincter ◽  
Cck Receptors ◽  
Physiological Assessment ◽  
Significant Attenuation

Rat gastric cholecystokinin (CCK) receptors are localized to the circular muscle layer of the pyloric sphincter, and a role for these receptors in the mediation of CCK satiety has been proposed. To directly assess the contribution of this receptor population in CCK satiety, the area of the pyloric sphincter containing these receptors was surgically removed, and the behavioral responses to CCK were compared pre- and postpylorectomy. The presence of CCK receptors in the gastroduodenal junction was assessed by either in vitro CCK receptor autoradiography or in vitro contractile response to CCK. The results depended on the time after pylorectomy during which testing occurred. Two to 3 wk after pylorectomy rats demonstrated a significant attenuation of CCK satiety such that while the response to 1 and 2 micrograms/kg was intact, any additional inhibition by 4 and 8 micrograms/kg was eliminated. At this time, no evidence of CCK receptors around the gastroduodenal junction was found. In contrast, 2-3 mo after pylorectomy, the normal dose-response inhibition to CCK was intact. Evidence for the presence of CCK binding sites at the gastroduodenal junction was found by both autoradiography and physiological assessment. These results indicate a role for pyloric CCK receptors in the mediation of CCK satiety.

Cholecystokinin downregulates receptors for vasoactive intestinal peptide and secretin in rat pancreatic acini

1990 ◽  
Vol 258 (3) ◽  
pp. G395-G403
Author(s):  
S. Katsushima ◽  
H. Adachi ◽  
T. Honda ◽  
S. Sato ◽  
T. Kusui ◽  
...  
Keyword(s):  
Vasoactive Intestinal Peptide ◽  
Binding Sites ◽  
Specific Binding ◽  
Amylase Secretion ◽  
Affinity Binding ◽  
Pancreatic Acini ◽  
Cck Receptors ◽  
Cyclic Monophosphate ◽  
Apparent Decrease ◽  
Specific Antagonist

We examined the effect of cholecystokinin (CCK) on the receptors for vasoactive intestinal peptide (VIP) and secretin in rat pancreatic acini. CCK decreased the specific binding of 125I-VIP and 125I-secretin by 42 and 51%, respectively. This CCK-induced inhibition was caused by an apparent decrease in the capacity of high-affinity binding sites of VIP and secretin receptors. CR 1409, a specific antagonist of CCK, abolished CCK-induced binding inhibition, whereas 12-O-tetradecanoylphorbol-13-acetate, A23187, and cycloheximide did not affect the binding of the radioligands. Both N2,O2-dibutyryl guanosine 3',5'-cyclic monophosphate (Bt2cGMP) and nitroprusside inhibited the specific binding of 125I-VIP. This inhibition, however, was because of an apparent decrease in the capacity of low-affinity binding sites on VIP receptors. CCK-induced downregulation of VIP and secretin receptors was associated with the diminished acinar response to VIP or secretin-induced adenosine 3',5'-cyclic monophosphate accumulation and amylase secretion, whereas neither Bt2cGMP nor nitroprusside affected VIP-induced amylase secretion. Data suggest that CCK-induced downregulation is mediated by the initial interaction of CCK with CCK receptors followed by some postreceptor process, which appears unrelated to protein kinase C, calcium mobilization, decrease in protein synthesis, or cellular cGMP increases. This downregulation, at least in part, accounts for CCK-induced restricted stimulation of amylase secretion by VIP and secretin.

Gastric loads potentiate inhibition of food intake produced by a cholecystokinin analogue

1991 ◽  
Vol 261 (5) ◽  
pp. R1141-R1146 ◽  
Author(s):  
G. J. Schwartz ◽  
L. A. Netterville ◽  
P. R. McHugh ◽  
T. H. Moran
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Threshold Dose ◽  
Gastric Distension ◽  
Cck Receptors ◽  
Load Combination ◽  
Glucose Intake ◽  
Dose Dependent Fashion ◽  
Inhibit Food Intake ◽  
Long Acting

We have proposed that cholecystokinin's (CCK) inhibition of gastric emptying contributes to its ability to inhibit food intake. To directly test this hypothesis in rats, the effect of the presence of a 5-ml gastric saline load on the ability of a long-acting cholecystokinin analogue U-67827E (0.1-10.0 nmol/kg) to inhibit intake of a 0.5 kcal/ml glucose solution was measured. The CCK analogue alone inhibited intake at a threshold dose of 2.5 nmol/kg. Although lower doses of the CCK analogue alone had no effect on subsequent glucose intake, when combined with the gastric load such doses did significantly inhibit intake. Thus the presence of a gastric load reduced the threshold dose of the CCK analogue required to inhibit intake. Furthermore, at suprathreshold doses, the peptide-load combination suppressed intake more than the peptide alone. In addition, administration of 0.5 and 5.0 nmol/kg doses of the CCK analogue inhibited gastric emptying at 10, 20, and 30 min in a dose-dependent fashion. The CCK analogue's inhibition of food intake and gastric emptying were reversed by pretreatment with 100 micrograms/kg L364,718, indicating that the analogue was having its effects by interacting with specific type A CCK receptors. Together these data support the notion that CCK satiety derives from an integration of the visceral afferent signals generated by CCK's promotion of gastric distension and those produced directly by CCK.

scholarly journals Leptin inhibits gastric emptying in rats: role of CCK receptors and vagal afferent fibers

2007 ◽  
pp. 315-322 ◽  
Author(s):  
B Çakır ◽  
Ö Kasımay ◽  
E Devseren ◽  
BÇ Yeğen
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Receptor Blocker ◽  
Adrenergic Blockade ◽  
Phenol Red ◽  
Gastric Emptying Rate ◽  
Cck Receptors ◽  
Afferent Fibers ◽  
Cephalic Phase ◽  
Vagal Afferent

Leptin regulates energy homeostasis and body weight by balancing energy intake and expenditure. It was recently reported that leptin, released into the gut lumen during the cephalic phase of gastric secretion, is capable of initiating intestinal nutrient absorption. Vagal afferent neurons also express receptors for both CCK and leptin, which are believed to interact in controlling food intake. The present study was undertaken to investigate the central and peripheral effects of leptin on gastric emptying rate. Under anesthesia, male Sprague-Dawley rats (250-300 g) were fitted with gastric Gregory cannulas (n=12) and some had additional cerebroventricular cannulas inserted into their right lateral ventricles. Following recovery, the rate of gastric emptying of saline (300 mOsm/kg H(2)O) was determined after instillation into the gastric fistula (3 ml, 37 degrees C, containing phenol red, 60 mg/l as a non-absorbable dilution marker). Gastric emptying rate was determined from the volume and phenol red concentrations recovered after 5 min. Leptin, injected intraperitoneally (i.p.; 10, 30, 60, 100 microg/kg) or intracerebroventricularly (i.c.v.; 5, 15 microg/rat) 15 min before the emptying, delayed gastric emptying rate of saline at the dose of 30 microg/kg or 15 microg/rat (p<0.001). When CCK(1) receptor blocker L-364,718 (1 mg/kg, i.p.), CCK(2) receptor blocker L-365,260 (1 mg/kg, ip) or adrenergic ganglion blocker bretylium tosylate (15 mg/kg, i.p.) was administered 15 min before ip leptin (30 microg/kg) injections, leptin-induced delay in gastric emptying was abolished only by the CCK(1) receptor blocker (p<0.001). However, the inhibitory effect of central leptin on gastric emptying was reversed by adrenergic blockade, but not by either CCK antagonists. Our results demonstrated that leptin delays gastric emptying. The peripheral effect of leptin on gastric motility appears to be mediated by CCK(1) receptors, suggesting the release of CCK and the involvement of vagal afferent fibers. On the other hand, the central effect of leptin on gastric emptying is likely to be mediated by adrenergic neurons. These results indicate the existence of a functional interaction between leptin and CCK receptors leading to inhibition of gastric emptying and short-term suppression of food intake, providing an additional feedback control in producing satiety.

Inhibitory effects of intestinal electrical stimulation on food intake, weight loss and gastric emptying in rats

2007 ◽  
Vol 293 (1) ◽  
pp. R78-R82 ◽  
Author(s):  
Jieyun Yin ◽  
Jing Zhang ◽  
Jiande DZ Chen
Keyword(s):  
Weight Loss ◽  
Electrical Stimulation ◽  
Gastric Emptying ◽  
Food Intake ◽  
Weight Change ◽  
Delayed Gastric Emptying ◽  
Control Diet ◽  
Control Group ◽  
Inhibitory Effects ◽  
Intestinal Electrical Stimulation

The aim was to investigate the effects of intestinal electrical stimulation (IES) on food intake, body weight, and gastric emptying in rats. An experiment on food intake and weight change was performed in 22 rats on a control diet and 10 diet-induced obese (DIO) rats for 4 wk with IES or sham IES. The effect of IES on gastric emptying was performed in another 20 rats in the control group. We found that 1) in control rats, 4-wk IES resulted in a reduction of 18.2% in the total amount of food intake compared with sham-IES ( P = 0.02); the rats treated with IES had a weight change of −1 ± 7.8g ( P = 0.03), which was equivalent to a weight loss of 6.2% due to IES when adjusted for normal growing. 2) Acute IES delayed gastric emptying by 20% in the control rats ( P < 0.01). 3) In the DIO rats, 1-wk IES with the same parameters as those used in the control rats resulted in a significant reduction in the total amount of food intake (126.6 ± 6.3 g vs. 116.9 ± 3.2 g, P < 0.01). More reduction in food intake was noted, and a significant weight change was also observed when stimulation energy was increased. 4) No adverse events were observed in any of the experiments. In conclusion, IES delays gastric emptying, reduces food intake, and decreases weight gain in control growing rats. These data suggest that it is worthy to explore therapeutic potentials of IES for obesity.

Blockade of type A, not type B, CCK receptors attenuates satiety actions of exogenous and endogenous CCK

1992 ◽  
Vol 262 (1) ◽  
pp. R46-R50 ◽  
Author(s):  
T. H. Moran ◽  
P. J. Ameglio ◽  
G. J. Schwartz ◽  
P. R. McHugh
Keyword(s):  
Food Intake ◽  
Glucose Consumption ◽  
Type A ◽  
Type B ◽  
Inhibitory Effects ◽  
Cck Receptors ◽  
Glucose Intake ◽  
Baseline Levels ◽  
Endogenous Release ◽  
Cck Receptor Antagonists

Recent work has suggested a role for an endogenous release of cholecystokinin (CCK) acting at either type A or type B CCK receptors in the control of food intake. In an effort to investigate whether the mechanisms by which exogenously administered and endogenously released CCK inhibits food intake are similar and depend upon interactions with either type A or type B CCK receptors, we examined in rats the ability of the type A (L 364718) and type B (L 365260) CCK receptor antagonists to 1) block the inhibition of glucose consumption produced by an intraperitoneal injection of 4 micrograms/kg of CCK and 2) increase glucose consumption in the absence of exogenous CCK after a 6-h daytime deprivation. Increasing dosages (10-100 micrograms/kg) of the type A CCK antagonist resulted in a dose-related blockade of the inhibition of intake produced by CCK, and the 100 micrograms/kg dose of the A antagonist significantly increased glucose intake above baseline levels. In contrast, no dose (10-1,000 micrograms/kg) of the B antagonist blocked the inhibitory action of exogenous CCK at any time point. In the absence of exogenous CCK, the 32 and 100 micrograms/kg doses of L 364718 increased intake above baseline levels. No dose (3.2-320 micrograms/kg) of the type B antagonist, L 365260, affected intake in this paradigm. These results suggest that the mediation of the feeding-inhibitory effects of exogenous and endogenous CCK are similar and depend upon activation of type A CCK receptors.

Development of cholecystokinin binding sites in rat upper gastrointestinal tract

1987 ◽  
Vol 252 (4) ◽  
pp. G529-G534 ◽  
Author(s):  
P. H. Robinson ◽  
T. H. Moran ◽  
M. Goldrich ◽  
P. R. McHugh
Keyword(s):  
Gastrointestinal Tract ◽  
Binding Sites ◽  
Specific Binding ◽  
Circular Muscle ◽  
Ingestive Behavior ◽  
Neonatal Rat ◽  
Upper Gastrointestinal Tract ◽  
Distal Stomach ◽  
Rat Fetus ◽  
Upper Gastrointestinal

Autoradiography using 125I-labeled Bolton Hunter-CCK-33 was used to study the distribution of cholecystokinin binding sites at different stages of development in the rat upper gastrointestinal tract. Cholecystokinin (CCK) binding was present in the distal stomach, esophagus, and gastroduodenal junction in the rat fetus of gestational age of 17 days. In the 20-day fetus, specific binding was found in the gastric mucosa, antral circular muscle, and pyloric sphincter. Mucosal binding declined during postnatal development and had disappeared by day 15. Antral binding declined sharply between day 10 and day 15 and disappeared by day 50. Pyloric muscle binding was present in fetal stomach and persisted in the adult. Pancreatic CCK binding was not observed before day 10. These results suggest that CCK may have a role in the control of gastric emptying and ingestive behavior in the neonatal rat.

Separable mechanisms for dorsal hindbrain CART peptide to inhibit gastric emptying and food intake

2003 ◽  
Vol 284 (6) ◽  
pp. R1418-R1426 ◽  
Author(s):  
Ulrika Smedh ◽  
Timothy H. Moran
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Corticotropin Releasing Factor ◽  
Sucrose Intake ◽  
Inhibitory Effects ◽  
Sucrose Consumption ◽  
Cart Peptide ◽  
Microstructure Parameters ◽  
Inhibit Food Intake ◽  
Dorsal Hindbrain

We investigated whether dorsal hindbrain and/or peripheral cocaine- and amphetamine-regulated transcript peptide (CARTp) acts to suppress gastric emptying of a caloric stimulus. Furthermore, effects of dorsal hindbrain CARTp on sucrose consumption and licking microstructure was studied, as well as the possible contribution of corticotropin-releasing factor (CRF) receptors to mediate effects of CARTp downstream on emptying and sucrose intake. Rats bearing gastric fistulas received intragastric infusions (1.0 ml/min) of 12 ml 12.5% glucose. Gastric samples were withdrawn immediately after the intragastric infusion to reflect emptying during gastric fill. CARTp injected in the fourth ventricle intracerebroventricularly (0.5 and 1.0 μg) suppressed gastric emptying. CARTp reduced sucrose intake at similar doses and altered a variety of lick microstructure variables (no. of licks, bursts, clusters, licks/burst, licks/clusters, interlick interval, first meal size, and first meal duration). Pretreatment with the CRF antagonist α-helical CRF-(9–41) blocked the effect of 1.0 μg CARTp on gastric emptying but not on sucrose consumed or on any of the licking microstructure parameters. These data demonstrate differential mediation of the feeding and gastric inhibitory effects of CARTp and suggest that CARTp-induced inhibition of gastric emptying does not contribute to this peptide's ability to inhibit food intake.

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