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1.
The rate and site of fluoride (F) absorption were compared in fasted 350 g male rats given 50 micrograms F (as NaF) in either water or a 7.5% pectin solution. Absorption was measured at intervals up to 2 h following gastric intubation. Gastric emptying was measured by inclusion of 14C-PEG in the F solution. The extent of gastric F absorption was derived from rates of gastric emptying (14C-PEG loss) and F loss. Pectin markedly slowed gastric emptying, but by 2 h, more than 90% of the solution had passed into the small intestine in both groups, and F absorption exceeded 90% in both groups. The rate of F absorption was initially much slower in the pectin group than in the group given F in water, and plasma F concentration increased more slowly and reached a lower maximum value. Absorption from the stomach was greater in the pectin group, but still accounted for only approx 25% of total gastrointestinal absorption. The reduced rate of F absorption and slower rise in plasma F concentration accompanying delayed gastric emptying indicate that passage of F into the small intestine is the major factor in rapid F absorption.  相似文献   

2.
The rate of paracetamol absorption depends on the rate of gastric emptying. Propantheline delayed gastric emptying and markedly slowed the absorption of paracetamol in six convalescent hospital patients. Conversely, the absorption of paracetamol in five healthy volunteers was accelerated by metoclopramide, a drug which stimulates gastric emptying. The total 24-hour urinary excretion of paracetamol was not influenced by propantheline or metoclopramide. Other similar absorption interactions probably occur since drugs are poorly absorbed from the stomach and many therapeutic agents influence gastrointestinal motility.  相似文献   

3.
Simultaneous intragastric administration of large doses of KCl (430 mg/kg and 860 mg/kg) with ethanol (4 g/kg) significantly reduces blood alcohol levels and diminishes manifestations of alcohol intoxication in rats. It was shown with parenteral administration of alcohol that the effect is not related to an acceleration of alcohol metabolism. Analysis of alcohol concentrations of gastric and intestinal content as well as in situ studies with animals whose stomachs were ligated at the pylorus revealed that KCl interferes with the absorption of alcohol through inhibition of gastric absorption and gastric emptying. The finding that equimolal concentrations of NaCl were unable to duplicate the described effects characterizes them as specific actions of the potassium ion.  相似文献   

4.
Mechanism of the aspirin-induced rise in blood alcohol levels   总被引:1,自引:0,他引:1  
Aspirin increases blood alcohol levels after post-prandial alcohol consumption in men. This was attributed to a decrease in first pass metabolism secondary to inhibition of gastric alcohol dehydrogenase. Since accelerated gastric emptying, decreased volume of distribution or delayed elimination could also result in higher blood alcohol levels, we investigated the effect of aspirin (1 g taken with a meal) on these parameters. Aspirin did not change the volume of ethanol distribution or the rate of its elimination. Moreover, it did not have a significant effect on gastric emptying. The half-time of 99Tc-DTPA loss was 65.5+/-5.4 minutes without and 71.3+/-6.5, with aspirin. Despite a trend for slower gastric emptying with aspirin, the alcohol bioavailability increased and was associated with a 39% decrease in the first pass metabolism of alcohol (from 106+/-4 to 65+/-19 mg/kg, p<0.05), consistent with the inhibition of gastric ADH activity. In keeping with this interpretation, the effect of aspirin was virtually absent in women, who have a much smaller first pass metabolism available for inhibition by aspirin.  相似文献   

5.
In previous studies on gastric emptying time in Limanda , data were obtained which predict that food will empty from the stomach according to: after a temperature sensitive delay. This curve gives an excellent prediction of the emptying of both artificial and natural food items given as single meals when stomachs are sampled directly. However, when two meals are given 3 h apart, emptying rate depends on whether the two meals remain separate or are allowed to mix by omitting the binding agent. In the absence of a binder, both meals are slowed so that the overall emptying rate is as predicted by the equation. When binder is present, the first meal is not delayed and the overall gastric emptying rate is increased 35%.  相似文献   

6.
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.  相似文献   

7.
The effects of several pharmacologically active amines on gastric emptying rate in male rats has been investigated. Of the compounds tested those with anticholinergic activity; amitriptyline, nortriptyline, imipramine, desmethylimipramine, 3-methylamino-1:1-diphenyl-prop-1-ene and its primary and tertiary amine analogues, dexamphetamine and methylamphetamine, all inhibited gastric emptying of a non-absorbable marker, polyethylene {1,2?14C} glycol. The compounds with little or no anticholinergic activity did not affect gastric emptying. The activity of the compounds in inhibiting gastric emptying falls in approximately the same order as their anticholinergic activity, lending support to the hypothesis that inhibition of gastric emptying is via in anti-cholinergic mechanism. The results also indicate that absorption is a prerequisite of activity in inhibiting gastric emptying and suggests that these compounds are not acting via a local mechanism.  相似文献   

8.
Pineal hormone melatonin is proposed as a potential treatment for severe sleep disturbances, and various gastrointestinal disorders. It was shown that melatonin increases intestinal motility and influences the activity of myoelectric complexes of the gut. The aim of the study was to evaluate the mechanisms of the effect of exogenous melatonin on gastric emptying rate. Male Sprague-Dawley rats were fitted with gastric cannulas under anesthesia. The rate of gastric emptying of saline was determined after instillation into the gastric fistula, from the volume and phenol red concentrations recovered after 5 min. Melatonin injected intraperitoneally (ip; 0.001-100 mg/kg) delayed gastric emptying rate of saline at 3 and 10 mg/kg doses. When administered ip 15 min before melatonin (10 mg/kg) injections, CCK2 (L-365,260, 1 mg/kg) or 5-HT3 receptor (ramosetrone, 50 microg/kg) blockers abolished melatonin-induced delay in gastric emptying rate, while the blockade of sympathetic ganglia (bretylium tosylate, 15 mg/kg) significantly reduced the delay in gastric emptying rate. CCK1 receptor blocker (L-364,718, 1 mg/kg) had no significant effect on the delaying action of melatonin. Our results indicate that pharmacological doses of melatonin delay gastric emptying via mechanisms that involve CCK2 and 5-HT3 receptors. Moreover, it appears that exogenous melatonin inhibits gastric motility in part by activating sympathetic neurons.  相似文献   

9.
The rate of appearance (R(a)) of exogenous glucose in plasma after glucose ingestion is presently measured by tracer techniques that cannot be used in standard clinical testing such as the oral glucose tolerance test (OGTT). We propose a mathematical model that represents in a simple way the gastric emptying, the transport of glucose along the intestinal tract, and its absorption from gut lumen into portal blood. The model gives the R(a) time course in terms of parameters with a physiological counterpart and provides an expression for the release of incretin hormones as related to glucose transit into gut lumen. Glucose absorption was represented by assuming two components related to a proximal and a distal transporter. Model performance was evaluated by numerical simulations. The model was then validated by fitting OGTT glucose and GLP-1 data in healthy controls and type 2 diabetic patients, and useful information was obtained for the rate of gastric emptying, the rate of glucose absorption, the R(a) profile, the insulin sensitivity, and the glucose effectiveness. Model-derived estimates of insulin sensitivity were well correlated (r = 0.929 in controls and 0.886 in diabetic patients) to data obtained from the euglycemic hyperinsulinemic clamp. Although the proposed OGTT analysis requires the measurement of an additional hormone concentration (GLP-1), it appears to be a reasonable choice since it avoids complex and expensive techniques, such as isotopes for glucose R(a) measurement and direct assessment of gastric emptying and intestinal transit, and gives additional correlated information, thus largely compensating for the extra expense.  相似文献   

10.
The aim of this study was to elucidate the variables of gastroduodenal motility determining gastric emptying. For this purpose the effects of exogenous cholecystokinin, secretin, and gastric inhibitory polypeptide on motility and gastric emptying were studied during a meal. Motility was measured with extraluminal strain gage force transducers and induction coils in unanaesthetized dogs. The pyloric diameter and the duodenal lumen were evaluated from radiographs. Gastric emptying of an acaloric cellulose meal was determined radiographically. When compared with control infusion of saline, cholecystokinin (1.7 Ivy units X kg-1 X h-1) and secretin (1.7 clinical units X kg-1 X h-1) delayed gastric emptying and diminished the force of the antral contractions, the force and frequency of the duodenal contractions, and opening of the pylorus. The contractile patterns of the duodenum were changed from propulsive to segmenting activity. Cholecystokinin additionally diminished the duodenal lumen. In contrast, gastric inhibitory polypeptide (1.5 microgram X kg-1 X h-1) did not influence gastroduodenal motility and gastric emptying. It is concluded that the motility parameters that were significantly altered by cholecystokinin and secretin are involved in the control of gastric emptying, while other parameters that remained unchanged play a minor role in the regulating process.  相似文献   

11.
Amylin is a 37-amino acid polypeptide co-secreted with insulin from the pancreatic beta-cells. It complements insulin's stimulation of the rate of glucose disappearance (Rd) by slowing the rate of glucose appearance (Ra) through several mechanisms, including an inhibition of mealtime glucagon secretion and a slowing of gastric emptying. To determine if endogenous amylin tonically inhibits these processes, we studied the effects of the amylin receptor blocker AC187 upon glucagon secretion during euglycemic, hyperinsulinemic clamps in Sprague-Dawley (HSD) rats, upon gastric emptying in HSD rats, and upon gastric emptying and plasma glucose profile in hyperamylinemic, and genetically obese, Lister Albany/NIH rats during a glucose challenge. Amylin blockade increased glucagon concentration, accelerated gastric emptying of liquids, and resulted in an exaggerated post-challenge glycemia. These data collectively indicate a physiologic role for amylin in glucose homeostasis via mechanisms that include regulation of glucagon secretion and gastric emptying.  相似文献   

12.
This study compared the physiological process of cholesterol absorption in different strains of inbred mice with the goal of identifying novel mechanism(s) by which cholesterol absorption can be controlled. The rate and amount of cholesterol absorption were evaluated based on [14C]cholesterol appearance in plasma after feeding a meal containing [14C]cholesterol and by the percentage of [14C]-cholesterol absorbed over a 24 h period. Results showed that the rate of [14C]cholesterol appearance in plasma was slower in 129P3/J mice than in SJL/J mice. However, more dietary cholesterol was absorbed over a 24 h period by 129P3/J mice than by SJL/J mice. In both strains of mice, cholesterol delivered with medium-chain triglyceride was absorbed less efficiently than cholesterol delivered with olive oil. The strain- and vehicle-dependent differences in cholesterol absorption efficiency correlated negatively with stomach-emptying rates. Furthermore, inhibition of gastric emptying with nitric oxide synthase inhibitor increased cholesterol absorption efficiency in SJL/J mice. These results document that stomach-emptying rate contributes directly to the rate of dietary cholesterol absorption, which is inversely correlated with the total amount of cholesterol absorbed from a single meal. Additionally, genetic factor(s) that influence gastric emptying may be an important determinant of cholesterol absorption efficiency.  相似文献   

13.
We investigated the effect of acarbose, an alpha-glucosidase and pancreatic alpha-amylase inhibitor, on gastric emptying of solid meals of varying nutrient composition and plasma responses of gut hormones. Gastric emptying was determined with scintigraphy in healthy subjects, and all studies were performed with and without 100 mg of acarbose, in random order, at least 1 wk apart. Acarbose did not alter the emptying of a carbohydrate-free meal, but it delayed emptying of a mixed meal and a carbohydrate-free meal given 2 h after sucrose ingestion. In meal groups with carbohydrates, acarbose attenuated responses of plasma insulin and glucose-dependent insulinotropic polypeptide (GIP) while augmenting responses of CCK, glucagon-like peptide-1 (GLP-1), and peptide YY (PYY). With mixed meal + acarbose, area under the curve (AUC) of gastric emptying was positively correlated with integrated plasma response of GLP-1 (r = 0.68, P < 0.02). With the carbohydrate-free meal after sucrose and acarbose ingestion, AUC of gastric emptying was negatively correlated with integrated plasma response of GIP, implying that prior alteration of carbohydrate absorption modifies gastric emptying of a meal. The results demonstrate that acarbose delays gastric emptying of solid meals and augments release of CCK, GLP-1, and PYY mainly by retarding/inhibiting carbohydrate absorption. Augmented GLP-1 release by acarbose appears to play a major role in the inhibition of gastric emptying of a mixed meal, whereas CCK and PYY may have contributory roles.  相似文献   

14.
1. Acute pre-treatment with either mannoheptulose or streptozotocin--both compounds acting as powerful suppressors of insulin secretion--caused a significant decrease on the in vivo rate of intestinal glucose absorption following an intragastric [U-14C]glucose administration. 2. Mannoheptulose treatment also lowered the rate of whole-body oxidation of the administered tracer. 3. Insulin had no effect on the metabolic fate of [U-14C]glucose by isolated enterocytes. 4. However, the rate of glucose uptake, measured by the oxidation of [1-14C]glucose to 14CO2 in the presence of phenazine methosulphate, was decreased by insulin at concentrations of 50-200 munits/ml. 5. In addition, the rate of transport of [U-14C]glucose by brush-border membrane vesicles was also inhibited by insulin at high concentrations (100-1000 munits/ml). 6. This indicated that insulin acts by inhibiting glucose transport in isolated in vitro preparations. 7. Acute pre-treatment with either mannoheptulose or streptozotocin caused a significant decrease in the rate of gastric emptying, measured as the distribution of [3H]insulin along the gastrointestinal tract, following an intragastric glucose load. 8. It is concluded that insulin secretion modulates intestinal glucose absorption in vivo by enhancing gastric emptying in spite of the inhibitory effects of glucose transport observed with in vitro preparations.  相似文献   

15.
16.
It is well established that duodenal acidification strongly inhibits gastric acid secretion, gastric emptying rate and gastrin release. These effects are at least partly mediated via hormonal pathways, but it is not known whether they are mediated by the release of one peptide named in the past enterogastrone, or by several peptides acting together. The effects of duodenal acidification on gastric acid secretion and gastrin release can be reproduced by infusion of small doses of secretin and plasma secretin levels increase during duodenal acidification or after a meal. This peptide is thus the most probable candidate as an enterogastrone. It has however never been clearly shown that administration of low doses of secretin do decrease gastric emptying rate as well as acid secretion. Experiments were performed on four dogs with gastric fistulas. A peptone solution was infused into the stomach. The experiments were repeated during infusion of synthetic secretin. Our results indicate that infusion of low doses of secretin reproduce all the effects of duodenal acidification: a significant inhibition of gastric acid secretion, gastrin release and gastric emptying rate.  相似文献   

17.
This study examined the rates of gastric emptying for water and 13 different carbohydrate-containing solutions in seven subjects, using conventional gastric intubation techniques. The rates of gastric emptying for water and a 10% glucose-polymer solution were also measured during 90 min of treadmill running at 75% of each subject's maximum oxygen consumption (VO2max). At rest, 15% glucose-polymer (P) and fructose (F) solutions emptied more rapidly from the stomach and provided a faster rate of carbohydrate delivery than did a 15% glucose (G) solution (p less than 0.05). The G solutions showed a constant energy delivery rate of 3.3 kcal.min-1; energy delivery from P and F solutions rose with increasing solution concentrations. The osmolality of the gastric aspirate predicted the rate of gastric emptying for all solutions (p less than 0.05) but overestimated rates of emptying for 10% and 15% P solutions and underestimated emptying rates for 10% and 15% F solutions. Exercise at 75% VO2max decreased the rate of gastric emptying of water but not of 10% P solutions. Thus the different rates of gastric emptying for different carbohydrate-containing solutions were not entirely explained by differences in osmolality. Furthermore, exercise may have different effects on the gastric emptying rates of water and carbohydrate solutions.  相似文献   

18.
We previously reported that MK-801 (dizocilpine), an antagonist of N-methyl-D-aspartate (NMDA)-type glutamate receptors, increased meal size and duration in rats. MK-801 did not increase sham feeding or attenuate reduction of sham feeding by intraintestinal nutrient infusions. These results suggested that the MK-801-induced increase in meal size did not depend on antagonism of postgastric satiety signals. Consequently, we hypothesized that the NMDA antagonist might increase food intake by directly antagonizing gastric mechanosensory signals or by accelerating gastric emptying, thereby reducing gastric mechanoreceptive feedback. To test this hypothesis, we recorded intake of 15% sucrose in rats implanted with pyloric cuffs that could be closed to prevent gastric emptying. Sucrose intake was increased when the pyloric cuffs were open, allowing the stomach to empty. However, intake was not increased when the pyloric cuffs were inflated, causing gastric retention of all ingested sucrose. Direct measurements of gastric emptying revealed that MK-801 accelerated the emptying of 5-ml loads of 0.9% NaCl and 15% sucrose. Furthermore, MK-801 also accelerated the rate of emptying of freely ingested sucrose regardless of the volume ingested. Taken together with our previous findings, these results indicate that blockade of NMDA receptors with MK-801 does not increase food intake by antagonizing gastric mechanosensation. Rather, it accelerates gastric emptying, and thereby may indirectly reduce gastric mechanoreceptive cues, resulting in prolongation of eating. Modulation of gastric emptying rate by NMDA receptors could play an important role in the control of meal sizes.  相似文献   

19.
Natriuretic peptides have been shown to decrease contractility of isolated gastric smooth muscle cells. However there is a paucity of research showing whether this effect has functional significance in the whole animal. The objective of this study was to test whether intravenously administered B-type Natriuretic Peptide (BNP) has an effect on gastric emptying and/or absorption in a whole animal mouse model. C57BL/6-Wild-type (WT) and Natriuretic Peptide Receptor type A (NPR-A) knockout (KO) mice were used in these studies. Gastric contractility was examined in anesthetized mice before and after BNP vs. vehicle injection. Gastric emptying of gavage fed 70 Kilo Dalton (kDa) FITC-dextran and absorption of 4 kDa FITC-dextran were compared in BNP vs. vehicle treated conscious WT and KO mice. BNP decreased gastric contractility (measured in change in intragastric pressure) from 2.26 +/- 0.29 to 1.44 +/- 0.11 mmHg (P < 0.05), pressure returned to 2.08 +/- 0.17 after 5 BNP half-lives (P < 0.05). There was no significant change in the vehicle or KO. BNP also decreased gastric emptying in WT mice compared to vehicle, 87.8 +/- 0.8% vs. 97.3 +/- 1.04% (P < 0.05) and this effect showed a dose-response relationship. In KO mice emptying was 95.8 +/- 0.5% (BNP) vs. 91.7 +/- 0.7% (Vehicle) (P > 0.05). The absorption in WT mice was 28.2 +/- 7.8 (relative fluorescence units) for BNP vs. 91 +/- 25.9 for vehicle (P < 0.05). For KO mice absorption was 64.3 +/- 14.9 for BNP vs. 60.6 +/- 17.4 for vehicle (P > 0.05). The results show that BNP decreases intragastric pressure, emptying and absorption by acting via the NPR-A receptor. We postulate that this effect is aimed at decreasing preload through decreased water and electrolyte absorption from the GI tract and may also be responsible for the symptoms of impaired gastrointestinal function observed in heart failure patients.  相似文献   

20.
Roles of pancreatic polypeptide in regulation of food intake   总被引:12,自引:0,他引:12  
Katsuura G  Asakawa A  Inui A 《Peptides》2002,23(2):323-329
Pancreatic polypeptide (PP) is produced in pancreatic islets of Langerhans and released into the circulation after ingestion of a meal. Peripherally administered PP suppresses food intake and gastric emptying. On the other hand, central administration of PP elicits food intake and gastric emptying. Therefore, PP actions on food intake may be, in part, attributable to gastric emptying. PP transgenic mice exhibit decreases in both food intake and gastric emptying rate that were clearly reversed by anti-PP antiserum. PP is an anorexigenic signal in the periphery and an orexigenic signal in the central nervous system.  相似文献   

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