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.

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.

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.

Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons

2003 ◽  
Vol 285 (2) ◽  
pp. R470-R478 ◽  
Author(s):  
Niels Vrang ◽  
Curtis B. Phifer ◽  
Michele M. Corkern ◽  
Hans-Rudolf Berthoud
Keyword(s):  
Food Intake ◽  
Mechanical Stimulus ◽  
Gastric Distension ◽  
Neural Pathways ◽  
Appetite Control ◽  
Balloon Distension ◽  
Different Types ◽  
Inhibit Food Intake ◽  
Freely Moving ◽  
Caudal Medulla

A group of neurons in the caudal nucleus of the solitary tract (NTS) processes preproglucagon to glucagon-like peptides (GLP)-1 and -2, peptides that inhibit food intake when administered intracerebroventricularly. The GLP-1/2-containing neural pathways have been suggested to play a role in taste aversion and nausea because LiCl activates these neurons, and LiCl-induced suppression of food intake can be blocked by the GLP-1 receptor antagonist exendin-9. As many gastrointestinal signals related to both satiety and nausea/illness travel via the vagus nerve to the caudal medulla, the present study assessed the capacity of different types of gastric distension (a purely mechanical stimulus) to activate GLP-1 neurons in the caudal NTS. Gastric balloon distension (1.4 ml/min first 5 min, 0.4 ml/min next 5 min, 9 ml total, held for 60 min) in nonanesthetized, freely moving rats produced 12- and 17-fold increases in c-Fos-expressing NTS neurons when distension was mainly in the fundus or corpus, respectively. Fundus and corpus distension increased the percentage of c-Fos-activated GLP-1 neurons to 21 ± 9% and 32 ± 5% compared with 1 ± 1% with sham distension ( P < 0.01). Thus gastric distension that may be considered within the physiological range activates GLP-1/2-containing neurons, suggesting some role in normal satiety. The results support the view that the medullary GLP system is involved in appetite control and is activated by stimuli within the behavioral continuum, ranging from satiety to nausea.

scholarly journals BZ043, a novel long-acting amylin analog, reduces gastric emptying, food intake, glycemia and insulin requirement in streptozotocin-induced diabetic rats

Peptides ◽  
2019 ◽  
Vol 114 ◽  
pp. 44-49 ◽  
Author(s):  
Caio Victor M.F. Nascimento ◽  
Celimar Sinezia ◽  
Thayna Sisnande ◽  
Luís Maurício T.R. Lima ◽  
Paulo G.S. Lacativa
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Insulin Requirement ◽  
Diabetic Rats ◽  
Long Acting

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.

Peptide YY(3–36) inhibits gastric emptying and produces acute reductions in food intake in rhesus monkeys

2005 ◽  
Vol 288 (2) ◽  
pp. R384-R388 ◽  
Author(s):  
Timothy H. Moran ◽  
Ulrika Smedh ◽  
Kimberly P. Kinzig ◽  
Karen A. Scott ◽  
Susan Knipp ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Rhesus Monkeys ◽  
Food Access ◽  
Peptide Yy ◽  
Human Subjects ◽  
Dose Range ◽  
Suppressive Effect ◽  
Reduce Food Intake ◽  
Inhibit Food Intake

Peptide YY3–36 [PYY(3–36)], a gastrointestinal peptide that is released into the circulation in response to ingesting a meal, has recently been suggested to play a role in controlling food intake. PYY(3–36) has been reported to inhibit food intake following peripheral administration in rodents and in human subjects. To more fully characterize the potential feeding actions of PYY(3–36), we examined the ability of a dose range of PYY(3–36) (0.3–3.0 nmol/kg) to affect liquid gastric emptying and daily 6-h food intake in male rhesus monkeys. Intramuscular PYY(3–36) produced a dose-related inhibition of saline gastric emptying that was maximal at a dose of 3 nmol/kg. Intramuscular PYY(3–36) administered before daily 6-h food access produced significant feeding reductions at doses of 1 and 3 nmol/kg. Analyses of the patterns of food intake across the 6-h period of food access revealed that PYY(3–36) increased the latency to the first meal and reduced average meal size without altering meal number. Although single doses of PYY(3–36) reduced intake, a suppressive effect on food intake was not sustained over multiple administrations across successive days. Together, these data suggest that PYY(3–36) has the ability to reduce food intake in acute test situations in nonhuman primates. Whether this is a physiological action of the endogenous peptide remains to be determined.

Intravenous infusion of glucagon-like peptide-1 potently inhibits food intake, sham feeding, and gastric emptying in rats

2005 ◽  
Vol 288 (6) ◽  
pp. R1695-R1706 ◽  
Author(s):  
Prasanth K. Chelikani ◽  
Alvin C. Haver ◽  
Roger D. Reidelberger
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Intravenous Infusion ◽  
Sham Feeding ◽  
Feeding Experiments ◽  
Intravenous Infusions ◽  
Inhibit Food Intake ◽  
Hormonal Signal ◽  
Glucagon Like Peptide ◽  
Glucagon Like Peptide 1

Glucagon-like peptide-1(7–36)-amide (GLP-1) is postulated to act as a hormonal signal from gut to brain to inhibit food intake and gastric emptying. A mixed-nutrient meal produces a 2 to 3-h increase in plasma GLP-1. We determined the effects of intravenous infusions of GLP-1 on food intake, sham feeding, and gastric emptying in rats to assess whether GLP-1 inhibits food intake, in part, by slowing gastric emptying. A 3-h intravenous infusion of GLP-1 (0.5–170 pmol·kg−1·min−1) at dark onset dose-dependently inhibited food intake in rats that were normally fed with a potency (mean effective dose) and efficacy (maximal % inhibition) of 23 pmol·kg−1·min−1 and 82%, respectively. Similar total doses of GLP-1 administered over a 15-min period were less potent and effective. In gastric emptying experiments, GLP-1 (1.7–50 pmol·kg−1·min−1) dose-dependently inhibited gastric emptying of saline and ingested chow with potencies of 18 and 6 pmol·kg−1·min−1 and maximal inhibitions of 74 and 83%, respectively. In sham-feeding experiments, GLP-1 (5–50 pmol·kg−1·min−1) dose-dependently reduced 15% aqueous sucrose intake in a similar manner when gastric cannulas were closed (real feeding) and open (sham feeding). These results demonstrate that intravenous infusions of GLP-1 dose-dependently inhibit food intake, sham feeding, and gastric emptying with a similar potency and efficacy. Thus GLP-1 may inhibit food intake in part by reducing gastric emptying, yet can also inhibit food intake independently of its action to reduce gastric emptying. It remains to be determined whether intravenous doses of GLP-1 that reproduce postprandial increases in plasma GLP-1 are sufficient to inhibit food intake and gastric emptying.

Effects of anorexigenic treatments on gastric motility in rats

1989 ◽  
Vol 256 (4) ◽  
pp. R955-R961 ◽  
Author(s):  
L. M. Flanagan ◽  
J. G. Verbalis ◽  
E. M. Stricker
Keyword(s):  
Food Intake ◽  
Gastric Motility ◽  
Gastric Distension ◽  
Reduce Food Intake ◽  
Inhibitory Effects ◽  
Gastric Function ◽  
Inhibit Food Intake ◽  
A Site ◽  
Gastric Contractions ◽  
Afferent Vagus

In these experiments we examined the effects on gastric motility of cholecystokinin, LiCl, hypertonic NaCl solution, gastric distension, and intraduodenal glucose loads, five dissimilar treatments known to reduce food intake in rats. In addition, we investigated whether any observed effects were dependent on the afferent vagus nerve by pretreating subjects with the neurotoxin capsaicin. Each of the five treatments virtually eliminated the gastric contractions seen after rats had consumed a large meal of chow; these effects were rapid in onset and continued for up to 30 min. The inhibitory effects of cholecystokinin and gastric distension were eliminated by pretreatment with capsaicin, whereas the effects of the other treatments were attenuated only slightly or not at all. Because most of these treatments have been shown to stimulate pituitary oxytocin secretion in rats as well as to inhibit food intake and gastric motility, these results are consistent with the hypothesis that the hypothalamic paraventricular nucleus is a site at which information is integrated in the coordinated control of food intake, gastric function, and neuroendocrine secretion.

Vagal afferent and efferent contributions to the inhibition of food intake by cholecystokinin

1997 ◽  
Vol 272 (4) ◽  
pp. R1245-R1251 ◽  
Author(s):  
T. H. Moran ◽  
A. R. Baldessarini ◽  
C. F. Salorio ◽  
T. Lowery ◽  
G. J. Schwartz
Keyword(s):  
Food Intake ◽  
Dose Range ◽  
Low Doses ◽  
Cck Receptors ◽  
Sham Surgery ◽  
Subdiaphragmatic Vagotomy ◽  
Glucose Intake ◽  
Vagal Afferent ◽  
Caudal Medulla

To assess the role of subdiaphragmatic vagal afferent and efferent fibers in the mediation of the inhibition of food intake by cholecystokinin (CCK), we compared the ability of a dose range (1-16 microg/kg), of CCK to affect 30-min liquid glucose (0.125 g/ml) intake in rats with either total subdiaphragmatic vagotomy, selective subdiaphragmatic vagal deafferentation, selective subdiaphragmatic vagal deefferentation, or sham surgery. Selective vagal deafferentation and deefferentations were produced by combinations of unilateral subdiaphragmatic vagotomy and contralateral afferent or efferent rootlet transection as fibers enter the caudal medulla. CCK produced a dose-related suppression of glucose intake in sham animals, and this action was eliminated in rats with total subdiaphragmatic vagotomy. CCK suppression of intake was attenuated in rats with vagal deafferentation, such that there was a loss of sensitivity to CCK. Vagal deefferentation resulted in lower levels of baseline intake and a truncation of the feeding-inhibitory actions of CCK. These data demonstrate that CCK's suppression of intake depends on actions of both vagal afferent and efferent fibers. We interpret these data as suggesting that 1) the actions of low doses of CCK depend on activation of vagal afferent CCK receptors and 2) the greater efficacy of higher CCK doses is the result of the potentiation of these vagal afferent actions due to local physiological gastrointestinal effects of the peptide that rely on vagal efferent input.

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