Gastric and nongastric mechanisms for satiety action of cholecystokinin

1988 ◽  
Vol 254 (4) ◽  
pp. R628-R632 ◽  
Author(s):  
T. H. Moran ◽  
P. R. McHugh
Keyword(s):  
Gastric Emptying ◽  
Linear Relationship ◽  
Inhibitory Action ◽  
Glucose Solution ◽  
Dose Range ◽  
Quantitative Relationship ◽  
Dilution Method ◽  
Sprague Dawley ◽  
Testing Period ◽  
Sprague Dawley Rats

The quantitative relationship between cholecystokinin's (CCK) inhibitory actions on gastric emptying and feeding was examined in rats. CCK (1, 2, 4, or 8 micrograms/kg) inhibited both the gastric emptying (determined by the dye dilution method) and ingestion of a 0.5-kcal/ml glucose solution in a 30-min testing period in 20-h deprived male Sprague-Dawley rats. Comparisons of the inhibitions of gastric emptying and feeding across the dose range of CCK revealed two components of CCK satiety: one defined by a linear relationship between the gastric inhibitory and feeding inhibitory actions of CCK through a dose range of 1-4 micrograms/kg, which accounted for 64% of the variability in the satiety action of CCK, and a second that appeared to be independent of the gastric inhibitory action of CCK.

Effect of caloric content and composition of a liquid meal on gastric emptying in the rat

1994 ◽  
Vol 267 (5) ◽  
pp. R1163-R1167 ◽  
Author(s):  
L. L. Maerz ◽  
H. Sankaran ◽  
S. J. Scharpf ◽  
C. W. Deveney
Keyword(s):  
Gastric Emptying ◽  
Gamma Camera ◽  
Casein Hydrolysate ◽  
Caloric Content ◽  
Diethylenetriaminepentaacetic Acid ◽  
Sprague Dawley ◽  
Substrate Composition ◽  
Liquid Meal ◽  
Time Points ◽  
Sprague Dawley Rats

We examined the effect of caloric content and substrate composition on gastric emptying in conscious Sprague-Dawley rats using gastric radioscintigraphy. Three-milliliter volumes of normal saline, glucose, casein hydrolysate, or intralipid containing 0, 1, 2, 3, or 6 kcal labeled with 99mTc-diethylenetriaminepentaacetic acid were given intragastrically. Gamma-camera imaging and computer analysis allowed construction of gastric emptying curves constructed over many time points for each emptying study. There was no difference in the half-emptying times (t1/2) between different substrates with equal calories, and increasing calories significantly prolonged gastric emptying for all substrates. Emptying occurred in a linear fashion with meals containing calories. With 3-ml meals containing 2, 3, or 6 kcal, the rate of delivery of calories to the duodenum is constant regardless of substrate or change in caloric content. We conclude that the rate of caloric delivery to the small intestine with gastric infusion of 1-6 kcal is relatively constant despite differences in total caloric load, substrate composition, and osmolarity.

scholarly journals Ghrelin improves burn-induced delayed gastrointestinal transit in rats

2007 ◽  
Vol 292 (1) ◽  
pp. R253-R257 ◽  
Author(s):  
H. S. Sallam ◽  
H. M. Oliveira ◽  
H. T. Gan ◽  
D. N. Herndon ◽  
J. D. Z. Chen
Keyword(s):  
Gastric Emptying ◽  
Burn Injury ◽  
Therapeutic Potential ◽  
Gastrointestinal Transit ◽  
Colonic Transit ◽  
Phenol Red ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Cholinergic Pathway ◽  
Upper Gastrointestinal

Delayed gastrointestinal transit is common in patients with severe burn. Ghrelin is a potent prokinetic peptide. We aimed at testing the effect of ghrelin on burn-induced delayed gastrointestinal transit in rats. Gastric emptying (GE), intestinal transit (IT), and colonic transit (CT) studies were performed in male Sprague-Dawley rats. Rats were randomized into two main groups as follows: sham injury and ghrelin-treated burn injury with doses of 0, 2, 5, and 10 nmol/rat ip 6 h after burn. Sham/burn injury was induced under anesthesia. Rats received a phenol red meal 20 min following ghrelin injection. Based on the most effective ghrelin dose, 1 mg/kg sc atropine was given 30 min before the ghrelin in one group of rats for each study. The rats in each group were killed 30–90 min later; their stomachs, intestines, and colons were harvested immediately, and the amount of phenol red recovered was measured. Percentage of gastric emptying (GE%) and geometric center for IT and CT were calculated. We found 1) severe cutaneous burn injury significantly delayed GE, IT, and CT compared with sham injury ( P < 0.05); 2) ghrelin normalized both GE and IT, but not the CT; 3) the most effective dose of ghrelin was 2 nmol/rat; and 4) atropine blocked the prokinetic effects of ghrelin on GE% and IT. In conclusion, ghrelin normalizes burn-induced delayed GE and IT but has no effect on CT in rats. The prokinetic effects of ghrelin are exerted via the cholinergic pathway. Ghrelin may have a therapeutic potential for burn patients with delayed upper gastrointestinal transit.

Augmented Reversal of Cisplatin-Induced Delayed Gastric Emptying by Amla (Emblica Officinalis) Fruit Extract in Sprague-Dawley Rats

2017 ◽  
Vol 15 (5) ◽  
pp. 684-691
Author(s):  
Asad Ahmad ◽  
Mohammad Khushtar ◽  
Ranjan Kumar ◽  
Badruddeen ◽  
Ambreena Riyaz ◽  
...  
Keyword(s):  
Gastric Emptying ◽  
Delayed Gastric Emptying ◽  
Emblica Officinalis ◽  
Sprague Dawley ◽  
Fruit Extract ◽  
Sprague Dawley Rats

scholarly journals Hyperosmolarity in the small intestine contributes to postprandial ghrelin suppression

2014 ◽  
Vol 306 (12) ◽  
pp. G1108-G1116 ◽  
Author(s):  
Joost Overduin ◽  
Tracy S. Tylee ◽  
R. Scott Frayo ◽  
David E. Cummings
Keyword(s):  
Small Intestine ◽  
Glucose Solution ◽  
Jugular Vein ◽  
Gastric Bypass Surgery ◽  
Sprague Dawley ◽  
Macronutrient Composition ◽  
Sprague Dawley Rats ◽  
Small Intestinal ◽  
The Impact ◽  
Dietary Modifications

Plasma levels of the orexigenic hormone ghrelin are suppressed by meals with an efficacy dependent on their macronutrient composition. We hypothesized that heterogeneity in osmolarity among macronutrient classes contributes to these differences. In three studies, the impact of small intestinal hyperosmolarity was examined in Sprague-Dawley rats. In study 1, isotonic, 2.5×, and 5× hypertonic solutions of several agents with diverse absorption and metabolism properties were infused duodenally at a physiological rate (3 ml/10 min). Jugular vein blood was sampled before and at 30, 60, 90, 120, 180, 240, and 300 min after infusion. Plasma ghrelin was suppressed dose dependently and most strongly by glucose. Hyperosmolar infusions of lactulose, which transits the small intestine unabsorbed, and 3- O-methylglucose (3- O-MG), which is absorbed like glucose but remains unmetabolized, also suppressed ghrelin. Glucose, but not lactulose or 3- O-MG, infusions increased plasma insulin. In study 2, intestinal infusions of hyperosmolar NaCl suppressed ghrelin, a response that was not attenuated by coinfusion with the neural blocker lidocaine. In study 3, we reconfirmed that the low-osmolar lipid emulsion Intralipid suppresses ghrelin more weakly than isocaloric (but hypertonic) glucose. Importantly, raising Intralipid's osmolarity to that of the glucose solution by nonabsorbable lactulose supplementation enhanced ghrelin suppression to that seen after glucose. Hyperosmolar ghrelin occurred particularly during the initial 3 postinfusion hours. We conclude that small intestinal hyperosmolarity 1) is sufficient to suppress ghrelin, 2) may combine with other postprandial mechanisms to suppress ghrelin, 3) might contribute to altered ghrelin regulation after gastric bypass surgery, and 4) may inform dietary modifications for metabolic health.

Inhibition of renin release by 14,15-epoxyeicosatrienoic acid in renal cortical slices

1990 ◽  
Vol 258 (2) ◽  
pp. E269-E274 ◽  
Author(s):  
W. L. Henrich ◽  
J. R. Falck ◽  
W. B. Campbell
Keyword(s):  
High Performance ◽  
Inhibitory Action ◽  
Rat Kidney ◽  
Renin Release ◽  
Gas Chromatography Mass Spectrometry ◽  
Epoxyeicosatrienoic Acid ◽  
Sprague Dawley ◽  
Cyclic Monophosphate ◽  
Sprague Dawley Rats ◽  
Cortical Slices

The effects of products of the cytochrome P-450 epoxygenase pathway of arachidonate metabolism on renin have not been previously examined. Initial high-performance liquid chromatography and gas chromatography-mass spectrometry studies documented the synthesis of four epoxyeicosatrienoic acid (EET) regioisomers of epoxygenase in superficial cortical slices from male Sprague-Dawley rats. Each regioisomer was tested for effects on both isoproterenol (ISO)-stimulated and basal renin secretion from cortical slices. ISO increased renin release significantly (169%, P less than 0.01) in all incubations; 14,15-EET (10(-6) M) significantly reduced this increase in stimulated renin release to 47%. The 5,6-, 8,9-, and 11,12-EETs did not significantly affect renin release. Basal renin release was not affected by any of the four EETs. To examine the mechanism of this inhibitory action, the effects of 14,15-EET on tissue adenosine 3',5'-cyclic monophosphate (cAMP) and guanosine 5'-cyclic monophosphate (cGMP) concentrations were measured. Tissue cAMP concentrations were sharply increased (4.75-fold, P less than 0.001) by ISO; 14,15-EET did not blunt this increase significantly. ISO and 14,15-EET did not affect tissue cGMP concentrations. Incubation of [14C]EET with cortical slices resulted in only 10% conversion of the 14,15-EET to 14,15-dihydroxyeicosatrienoic acid (DHET) (diol) after 90 min; no other metabolites were observed. The 14,15 DHET did not alter either basal or stimulated renin release. These studies document the synthesis of EETs in rat kidney and demonstrate a direct effect of the 14,15-EET to inhibit stimulated renin release. This inhibitory action occurs without an effect on tissue cAMP or cGMP concentrations.

Leptin-induced decrease in food intake is not associated with changes in gastric emptying in lean mice

1997 ◽  
Vol 272 (3) ◽  
pp. R1007-R1011 ◽  
Author(s):  
M. D. Barrachina ◽  
V. Martinez ◽  
J. Y. Wei ◽  
Y. Tache
Keyword(s):  
Gastric Emptying ◽  
Food Intake ◽  
Intraperitoneal Injection ◽  
Acute Effect ◽  
Free Access ◽  
Sprague Dawley ◽  
Single Intraperitoneal Injection ◽  
Recombinant Mouse ◽  
Purina Chow ◽  
Sprague Dawley Rats

Chronic treatment with leptin regulates body weight and energy balance and reduces food intake in obese and lean mice. In 18- to 20-h fasted lean mice (C57BL/6, +/+), we examined the acute effect of a single intraperitoneal injection of recombinant mouse leptin (0.12 mg/kg) on food intake and gastric emptying. Leptin reduced food intake, with a peak inhibition at the 5th h postinjection (69 +/- 12%/h), although there was no change in food consumption at the 1st h. Leptin did not alter the 4-h rate of gastric emptying of a solid nutrient meal (free access to Purina chow for either 1-, 2-, or 4-h period). In normal Sprague-Dawley rats fasted for 18-20 h, a single intraperitoneal injection of recombinant mouse leptin (0.2 or 1.2 mg/kg) did not modify the 7-h cumulative or hourly food intake. These results show that a single intraperitoneal injection of recombinant mouse leptin reduces food intake within 5 h while not influencing gastric emptying of ingested food in lean mice. Sprague-Dawley rats are unresponsive to the food intake-reducing effect of a single intraperitoneal injection of mouse leptin at a dose 10-fold higher than that shown to be effective in mice within the first 4-7 h postinjection.

Circulating angiotensin II and drinking behavior in rats

1990 ◽  
Vol 259 (3) ◽  
pp. R531-R538 ◽  
Author(s):  
C. M. Pawloski ◽  
G. D. Fink
Keyword(s):  
Angiotensin Ii ◽  
Water Intake ◽  
Dose Range ◽  
Drinking Behavior ◽  
Ang Ii ◽  
Sprague Dawley ◽  
Physiological Conditions ◽  
Water Drinking ◽  
Sprague Dawley Rats ◽  
Before And After

This study was designed to investigate the effects on water drinking of acute and chronic increases in circulating angiotensin II (ANG II) concentrations in rats. Experiments were conducted in male Sprague-Dawley rats chronically instrumented with femoral arterial and venous catheters and permanently housed in metal metabolism cages. ANG II was infused intravenously either acutely (30 min-2 h) or chronically (3 days) in a dose range of 10-60 ng/min. In no instance did such infusions cause a statistically significant increase in water intake. Other experiments examined the influence of ANG II (10 ng/min iv) on drinking elicited by infusion of hypertonic sodium chloride (1.5 M at 3.5 microliters/min). ANG II administration did not increase drinking to a hypertonic saline stimulus or lower the osmotic threshold for drinking. Nitroprusside (12 micrograms/min) was infused for 30 min to produce hypotension and drinking. Water intake associated with this stimulus was not changed by blocking ANG II formation with enalapril (2 mg/kg iv) or by concomitant infusion of ANG II (10 ng/min iv). Finally, plasma ANG II concentrations were measured before and after 1-h intravenous infusion of saline or ANG II to determine the levels of circulating ANG II produced by the infusion rates used here. It is concluded that the range of circulating ANG II concentrations found under most physiological conditions in rats does not directly stimulate drinking or participate importantly in osmotic or hypotension-induced drinking.

Flunitrazepam variably alters morphine, buprenorphine, and methadone lethality in the rat

2002 ◽  
Vol 21 (11) ◽  
pp. 599-605 ◽  
Author(s):  
S W Borron ◽  
C Monier ◽  
P Risède ◽  
F J Baud
Keyword(s):  
Drug Interactions ◽  
Respiratory Depression ◽  
Lethal Dose ◽  
Quantitative Relationship ◽  
Mechanistic Studies ◽  
Sprague Dawley ◽  
Time To Death ◽  
Median Lethal Dose ◽  
Prolonged Time ◽  
Sprague Dawley Rats

Opiates and substitution products are frequently abused, alone and in association with benzodiazepines. While this combination may result in severe respiratory depression and death, the quantitative relationship remains uncertain. We performed randomized, blinded intravenous median lethal dose (MLD) studies in Sprague–Dawley rats of morphine, buprenorphine, and methadone, alone and in combination with intraperitoneal flunitrazepam pretreatment. We employed the up-and-down method, performed in quadruplicate, comparing time to death following opioid injection. Results are expressed as median of four series (extremes). The MLDs of morphine, buprenorphine, and methadone alone were 64.0 (33.6:79.5), 234.6 (168.6:284.4), and 22.5 (19.3:24.1) mg/kg, respectively, and 60.6 (35.2:88.2), 38.4 (30.6:54.0), and 13.0 (9.7:13.8) mg/kg, respectively, after pretreatment with 40 mg/kg flunitrazepam. Times to death for morphine, buprenorphine, and methadone alone were 2.5 (0.8:24), 0.02 (0.0:24), and 2.0 (0.0:24) hours, respectively, and 13.5 (0.0:144), 24.0 (0.0:120), and 0.0 (0.0:24) hours, respectively, after pretreatment with flunitrazepam 40 mg/kg, ip. Flunitrazepam significantly altered methadone (P=0.02) and buprenorphine (P=0.02) but not morphine lethality (P=0.77). Flunitrazepam significantly prolonged time to death only for buprenorphine (P<0.01). Flunitrazepam–opioid drug–drug interactions are more complex than is generally believed. Mechanistic studies of flunitrazepam–opioid lethal interactions are needed.

Subchronic Toxicity and Developmental Toxicity Studies in Rats With Aquateric® Aqueous Enteric Coating

1999 ◽  
Vol 18 (2) ◽  
pp. 109-116 ◽  
Author(s):  
Lois A. Kotkoskie ◽  
Christine Freeman ◽  
Mark A. Palmieri
Keyword(s):  
Developmental Toxicity ◽  
Dose Range ◽  
Clinical Signs ◽  
Study Groups ◽  
Feed Consumption ◽  
Histological Evaluation ◽  
Sprague Dawley ◽  
Enteric Coating ◽  
Toxicological Effects ◽  
Sprague Dawley Rats

Studies were conducted to evaluate the subchronic and developmental toxicity of Aquateric® Aqueous Enteric Coating. Homogeneity and stability studies were conducted over a range of 5,000 to 50,000 ppm Aquateric in the diet. In the subchronic study, groups of Sprague-Dawley rats (20/sex/group) received 0 (control), 5,000, 25,000, or 50,000 ppm Aquateric in the diet for 90 consecutive days. No mortality, clinical signs of toxicity or adverse toxicological effects on hematology or serum chemistry parameters, body weights, feed consumption, ophthalmological examinations, or histological evaluation of tissues were noted in any treatment group. In the developmental toxicity study, groups of pregnant Sprague-Dawley rats (25/group) received 0 (control), 5,000, 25,000 or 50,000 ppm Aquateric in the diet on gestational days 6-15. No evidence of maternal toxicity or fetotoxicity or embryotoxicity was noted. The no observed adverse effect level (NOAEL) exceeds 50,000 ppm in the diet, which represents a dose range of approximately 3600 to 4100 mg/kg/day. The results of these studies demonstrate the low toxicity of Aquateric. The estimated human intake is approximately 4 mg/kg/day. Based on the NOAEL from the subchronic study of 3604 mg/kg/day, the margin of safety is 900.

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