A central site of dopamine agonist action to modify gastric secretion in the rat

2-Di-n-propylamino-5,6-dihydroxytetralin (tetralin) administered subcutaneously (6.25-25 micrograms/kg s.c.) or into the cerebral ventricles (i.c.v. 0.5-10 micrograms) dose-dependently reduced the volume and acid concentration of gastric secretion collected from rats having chronically implanted gastric and intracerebral cannulas. Apomorphine or dopamine given i.c.v. also reduced gastric secretory volume and acid concentration. Tetralin-induced reductions (s.c. or i.c.v.) in gastric acid concentrations were antagonised by the dopamine antagonists metoclopramide, sulpiride or haloperidol and by the alpha 2-adrenoceptor antagonist yohimbine given systemically or i.c.v. The alpha 2-adrenoceptor antagonist idazoxan or the beta-adrenoceptor antagonist propranolol (i.c.v.) also antagonised the tetralin-induced (i.c.v.) reduction in gastric acid concentration. In contrast, the reduction in gastric secretory volume effected by centrally or peripherally administered tetralin could only be antagonised by propranolol. Previous observations that apomorphine can reduce gastric secretory volume and acid concentration are thus extended to 2-di-n-propylamino-5,6-dihydroxytetralin. Both agents reduce gastric secretory volume via an action on beta-adrenoceptors, and reduce gastric acid concentration via dopamine receptors, with alpha 2-adrenoceptor and, more speculatively, beta-adrenoceptor mechanisms contributing to the effect of the tetralin compound. These actions may be mediated, at least in part, via central mechanisms.     

An analysis of the hypothalamic sites at which substituted benzamide drugs act to facilitate gastric emptying in the guinea-pig

An analysis of the hypothalamic sites at which the substituted benzamides, metoclopramide and clebopride, act to facilitate gastric emptying was undertaken in the guinea-pig. Standard stereotaxic techniques for intracerebral injection via chronically indwelling intracerebral guides were combined with measurement of gastric emptying by fluoroscopic following of the passage of barium sulphate spheroids from the stomach. Injections were made at 7 different locations within the hypothalamus at Ant. 8.0, 8.9 and 9.6, Lat. +/- 1.0, +/- 1.6, +/- 2.2 (relative to the stereotaxic frame) and at 7.0, 8.0 and 9.0 mm below guide tips in the cortex. The most sensitive sites for gastric facilitation by the substituted benzamides were located at Ant. 8.9, Lat. +/- 1.6, Vert. -8.0, -9.0, the "perifornical area". As the distance of the injection site from the area of the fornix increased, so the facilitatory gastric action diminished, with marked delays or loss in response occurring when injection sites were moved 1 mm above, 0.6 mm lateral, 0.4 mm medial, 0.9 mm posterior or 0.7 mm anterior. The facilitatory gastric actions of metoclopramide and clebopride in the perifornical area of the hypothalamus were not mimicked by haloperidol, domperidone or sulpiride. Atropine, injected into the hypothalamus, markedly reduced gastric emptying; hexamethonium was less effective, and phentolamine, propranolol and methysergide were inactive. Atropine (but not hexamethonium, phentolamine, propranolol or methysergide), injected into the hypothalamus, dose-dependently antagonised the facilitatory gastric action of metoclopramide injected at the same site. Carbachol (but not serotonin, noradrenaline, dopamine or apomorphine), injected into the perifornical area, caused marked facilitation of gastric emptying.(ABSTRACT TRUNCATED AT 250 WORDS)     

NECA-induced hypomotility in mice: evidence for a predominantly central site of action

The behavioral effects of four adenosine analogues (NECA, CHA, CPA and CV-1808) were investigated in mice using a holeboard test, which measures both directed exploration (head-dipping) and a locomotor activity. NECA, CHA and CPA showed significant dose-related reductions in all the holeboard measures (NECA much greater than CHA = CPA), whilst CV-1808 showed no significant effect on any of the measures over the dose range tested. In a subsequent experiment NECA-induced hypomotility was attenuated by the adenosine receptor antagonists, theophylline (which is both centrally and peripherally active) and, though to a lesser extent, by the adenosine receptor antagonist 8-(p-sulfophenyl)theophylline (8-pSPT), which poorly penetrates the blood-brain barrier. The results suggest that NECA-induced hypomotility may be predominantly mediated centrally since the centrally active antagonist was the most effective in reversing the effect, however, peripheral mechanisms may also play a role since equimolar concentrations of 8-pSPT elicit some reversal of NECA-induced hypomotility.     

The action of cisapride on gastric emptying and the pharmacodynamics and pharmacokinetics of oral diazepam

Summary The effects of the benzamide cisapride (C) (8 mg) i.v. have been compared to placebo (P) in a double blind randomised study. The effects on gastric emptying, the absorption and effects of oral diazepam, and BP and pulse were observed.Cisapride increased the rate of gastric emptying of 500 ml liquid containing diazepam 10 mg (t_1/2 C: 7.4 min, P: 14.9 min). The initial rate of absorption of diazepam contained in the drink was increased by C (AUC 0–1 h C: 328 µg h 1^–1, P: 253 µg h 1^–1, but there was no change in overall bioavailability. This change in diazepam kinetics was associated with a significantly greater impairment in reaction time in the first 45 min after drinking but not in self rated sedation. Cisapride produced a significant tachycardia (e.g. after 10 min C: 82 beats/min, P: 69 beats/min) which probably reflects a peripheral vasodilator action. Cisapride may therefore alter the pharmacokinetics and dynamics of concurrently administered drugs.     

The action of cysteamine and synkavit on gastric emptying in the normal and irradiated rat

A radiographic method for studying the delay in gastric emptying in the rat caused by whole body irradiation has been applied to the investigation of two compounds which modify the effects of irradiation. The method may be of general use in the study of the action of drugs. Synkavit, which can potentiate the lethal effects of irradiation on tumours, caused a delay in gastric emptying. When Synkavit and irradiation were combined, a simple summation of the delays produced by each of these agents occurred. Cysteamine, which gives some protection against the lethal action of x-rays, also caused a delay in gastric emptying. It did not protect against the action of x-rays on stomach emptying.     

Morphine reduces vagal-stimulated gastric acid secretion through a central action

The influence of morphine on gastric acid secretion stimulated by 2-deoxy-D-glucose or electrical vagal stimulation was studied in anaesthetised rats with perfused stomachs. It was found that changes in gastric acid output induced by electrical vagal stimulation were not noticeably affected, whereas those evoked by 2-deoxy-D-glucose were significantly suppressed by morphine pretreatment. The depressant effect of the opiate on the acid secretion stimulated by 2-deoxy-D-glucose was abolished by naloxone pretreatment. It is suggested that morphine inhibits vagal-stimulated gastric acid secretion in rats by acting predominantly on opioid receptors in the central nervous system.     

胰头十二指肠切除术后胃排空延迟及严重程度的 影响因素分析

目的探讨胰头十二指肠切除术后胃排空延迟及严重程度的发生情况及影响因素。方法选择 2013年 1月至 2017年 10月在平煤神马医疗集团总医院行胰头十二指肠切除术病人 156例的临床资料进行回顾性分析。分析影响胃排空延迟的影响因素、影响胃排空延迟不同严重程度的相关因素。结果多因素分析结果显示胃空肠吻合方式 Roux?en?Y法、管型吻合器直径 28 mm是保护因素,保留幽门、术中出血量 ≥1 000 mL、术后白蛋白水平＜ 30 g/L,术后腹部并发症是胃排空延迟的高危因素( P＜0.05);年龄 ≥65岁、术后腹部并发症是影响胃排空延迟严重程度的独立危险因素( P＜0.05)。结论 Roux?en?Y法胃空肠吻合、管型吻合器直径 28 mm可降低胃排空延迟的风险,保留幽门、术中出血量 ≥1 000 mL、术后白蛋白水平＜ 30 g/L,术后腹部并发症增加胃排空延迟的风险;年龄≥65岁、术后腹部并发症是影响胃空肠排空延迟严重程度的独立危险因素。     

不透X线标志物检测胃排空对糖尿病胃轻瘫诊断试验的评价

目的评价不透X线标志物（ROMs）检测胃排空对糖尿病胃轻瘫的诊断效能及应用价值。方法对50例2型糖尿病患者采用ROMs法与核素显像法进行胃排空测定。分别记录6h胃排空率（GER）和胃半排空时间（GEt1/2），分析ROMs法诊断的敏感性与特异度。结果ROMs法6h胃排空率为100％时，敏感度、特异度分别为88．9％和81．3％；6h胃排空率为90％时，敏感度、特异度分别为72．2％和93．8％。受试者工作特性曲线下面积为0．884，Kappa值为0．67，糖尿病胃轻瘫发生率44％（22／50）。结论ROMs和核素显像检测胃排空具有良好的相关性，与金标准（核素显像）比较，ROMs法具有较高的特异度、准确度和Kappa值，一致性和信度好，且较简便，检测费用较低，适合糖尿病胃轻瘫的人群流行病学调查或社区发病学调查。     

A mouse model for assessing the impact of ingested nutrients on gastric emptying rate

1. The nutrient content of meals can affect the rate of gastric emptying. The aim of the present study was to assess whether the gastric emptying breath test could detect nutrient-induced delays in gastric emptying. 2. Following ingestion of a non-nutrient, carbohydrate- or lipid-containing liquid, mice were placed into chambers and breath samples were collected at intervals. Analysis of the rate of (13)CO(2) excretion allowed the calculation of gastric half-excretion time. 3. Gastric half-excretion time was significantly delayed by the incorporation of carbohydrate or lipid into the test liquid. 4. The present study has shown that the breath test is sensitive enough to detect changes induced by altering the nutrient and caloric content of test meals.     

Direct evidence for central action of PCPGABA to stimulate gastric acid secretion by intracisternal injection

PCPGABA, injected into the cisterna magna, significantly stimulated gastric acid secretion in the perfused rat stomach preparation. This secretagogue action was dose-dependent (0.5-2 micrograms/rat). The peak response occurred within 60 min and lasted up to 100 min. The secretagogue action by PCPGABA was completely reduced by truncal vagotomy. Intracisternal injection of 5-aminovaleric acid, a GABAB-receptor antagonist, did not alter basal gastric acid output, and it also failed to antagonize the acid secretory response to intracisternal PCPGABA. These results demonstrate that intracisternal PCPGABA caused hypersecretion of acid through vagal dependent mechanisms partially independent of GABAB-receptors.     

Delay of gastric emptying by duodenal intubation: sensitive measurement of gastric emptying by the paracetamol absorption test

AIMS: To examine the influence of duodenal intubation on gastric emptying measured by the paracetamol absorption test using a new algorithm developed to estimate emptying parameters, and to determine the sensitivity of this test. METHODS: A caloric liquid meal with paracetamol as marker of emptying was administered orally to eight healthy volunteers during phase I and phase II of the migrating motor complex (MMC) and without intubation on 3 separate days, and to 10 patients with partial gastrectomy. RESULTS: Healthy subjects: With duodenal tube, time until 25% of the meal had emptied (t25%) was 24+/-7 (phase I, P<0.02) and 21+/-6 min (phase II, P<0.02) compared with 14+/-4 min for meal intake without intubation. Time until 50% of the meal had emptied (t50%) was 45+/-8 (phase I, P<0.001) and 35+/-8 min (phase II, P<0.02) compared with 26+/-9 min for meal intake without intubation. Intraduodenal instillation of 10-20 mL of the liquid meal was reliably detected. Patients: In 9 out of 10 patients with partial gastrectomy t25% was below the lower limit of the range for healthy controls, and t25% detected accelerated emptying with a higher degree of sensitivity than the commonly applied pharmacokinetic parameters Cmax and Tmax. CONCLUSIONS: A duodenal tube delays gastric emptying of a caloric liquid meal. The paracetamol absorption test emerges as a sensitive method suitable for detecting both delayed and accelerated gastric emptying of caloric liquid meals.     

The central site of the sympatho-inhibitory action of 5-hydroxytryptamine in the cat

The aim of this study was to determine the site in the CNS at which 5-hydroxytryptamine (5-HT) inhibits efferent sympathetic nerve activity in the cat. 5-Hydroxytryptamine (3 and 10 micrograms/kg), given into the lateral cerebral ventricle, produced immediate non dose related increases in mean blood pressure (MBP), heart rate (HR) and renal nerve activity (RNA). Larger doses (30 and 100 micrograms/kg i.c.v.) produced gradual decreases in blood pressure, heart rate and renal nerve activity, which did not occur when access of the drug to the fourth ventricle was prevented. Administration of 5-HT (10 and 30 micrograms/kg) into the fourth ventricle produced only decreases in blood pressure, heart rate and renal nerve activity after 15-40 min, which were accompanied by decreases in cardiac output and renal vascular resistance, but little or no change in total peripheral resistance. Application of 5-HT onto the ventral surface of the medulla, into the subarachnoid space at various levels along the spinal cord or into various parts of the nucleus tractus solitarius produced no effect on blood pressure heart rate or renal nerve activity. However, application of a cotton wool pledget soaked in a 5-HT solution (3 mg/ml) over the entire obex/NTS region produced immediate decreases in blood pressure, heart rate and renal nerve activity. These studies suggest that the sympatho-inhibitory effect of 5-HT is due to an action at a site near the caudal end of the dorsal surface of the medulla.     

The gastric emptying of hard gelatin capsules

The gastric emptying of hard gelatin capsules has been studied by labelling the powder- fill of the capsules, and visualizing externally usins, a gamma camera. Capsules whcih disperse well in vitro, disperse and empty rapidly in vivo significantly faster after a meal containing a high liqauid content than on a fastirg stomaoh (P<0.01). Relatively poorly dispersing capsules, and readily soluble materials behave similarly in both fasting and non-fasting conditions. The capsules which disprse poorly in vitro do not disperse in vivo and empty into the duodenum undispersed. The readily soluble capsules dissolve and empty rapidly irrespective of the condition of the stomach.     

Central site of inhibitory action of bombesin on gastric acid secretion in rats

Sites of inhibitory action of bombesin on gastric acid secretion were examined in rats anesthetized with urethane. Intracerebroventricular administration of bombesin (3-1000 pmole) dose-dependently inhibited the increase in gastric acid secretion induced by electrical stimulation of the vagus nerve (1 mA, 0.5 msec, 3 Hz). On the other hand, intrathecal (direct lumbar puncture) administration of bombesin, even in the large dose of 1 nmole, had no effect on the vagally stimulated gastric acid secretion. Three pmoles of bombesin microinjected into the preoptic area, the anterior hypothalamus and the paraventricular nucleus inhibited the vagus stimulated gastric acid secretion. Microinjection of this peptide into the ventromedial nucleus, the dorsomedial nucleus and the lateral hypothalamic area were without effect. A large electrolytic lesion of the anterior hypothalamus, including the preoptic-anterior hypothalamic area and the paraventricular nucleus, abolished the inhibitory effect of intracerebroventricularly applied bombesin, but a lesion restricted to the preoptic-anterior hypothalamus or the paraventricular nucleus was without effect. We propose that the preoptic area, the anterior hypothalamus and the paraventricular nucleus are all involved in the inhibitory effect of bombesin on gastric acid secretion.     

An assessment of gastric emptying by breathalyser

1 A breathalyser has been used to measure blood alcohol levels at short intervals to produce an absorption curve which we have shown is reproducible.

2 Changes in the rate of absorption which reflect changes in gastric emptying times produced by metoclopromide and propantheline have been demonstrated.

3 The breathalyser technique described appears to offer a simple method of studying the effects of drugs on the rate of gastric emptying.

     

Misoprostol-inhibited rat gastric emptying is independent of gastric inhibitory polypeptide release

We studied the effects of orally or intraperitoneally administrated misoprostol on rat gastric emptying and looked what was the role of gastric inhibitory polypeptide (GIP) in this emptying. The rats initially received oral misoprostol at doses of 1, 10, 50, and 100 microg/kg. Another group of rats received misoprostol intraperitonally at doses of 10, 50, 250, and 500 microg/kg. Using an oral radiochromium motility marker, the liquid gastric emptying was measurement 30 min after misoprostol treatment. The plasma GIP levels were measured by a home-made radioimmunoassay kit. Oral treatments at the doses of 1 and 10 microg/kg did not influence emptying, whereas other doses delayed emptying (p < 0.01). Except the 10- microg/kg injection, other doses exhibited a dose-dependent inhibition in emptying (p < 0.01). Neither oral feeding nor intraperitoneal injection changed plasma GIP levels. We conclude that liquid gastric emptying is disturbed after various routes of misoprostol treatment; GIP appears less important in the misoprostol-mediated gastric emptying.     

A possible intraneuronal site of action of thymoleptics

The uptake of catecholamines (CAs) into crude mitochondria preparations (P₂ fractions) and vesicle preparations from rat hypothalamus and striatum were compared in terms of the inhibition by thymoleptics and other drugs.Thymoleptics preferentially inhibited the uptake of CAs into hypothalamic P₂ fractions, while ATPase inhibitors preferentially inhibited the uptake of dopamine into striatal P₂ fractions. When the preparation obtained from rats pretreated with reserpine was used, the preferential inhibition of hypothalamic uptake by thymoleptics was entirely abolished. When P₂ fractions from both regions were incubated with 10^-6M ¹⁴C-imipramine, the intrasynaptosomal distribution of labeled imipramine revealed its affinity not only to the synaptosomal membrane, but also to the synaptic vesicles. Accumulated ³H-norepinephrine (NE) could be released by a hypoosomotic shock from striatal P₂ fractions, but not from hypothalamic P₂ fractions. The ATP-Mg²⁺-dependent uptake of ³H-NE into the synaptic vesicles from rat brain stem was inhibited by desipramine.These results indicate that the inhibition of CA uptake by thymoleptics in the hypothalamus is predominantly due to the inhibition at the synaptic vesicle, while in the striatum the uptake at the synaptosomal membrane is predominantly inhibited.     

Clonidine inhibition of pancreatic secretion in rats: a possible central site of action

The effects of clonidine on pancreatic secretion were studied in rats fitted with chronic or acute fistulas. Subcutaneous and intracerebroventricular injections of clonidine in conscious rats induced a dose-dependent inhibition of basal pancreatic secretion involving volume, bicarbonate output and protein output with an ED50 of about 10 micrograms/kg. Clonidine inhibition of pancreatic secretion was not dependent on the associated inhibition of gastric acid output. In conscious rats, the pancreatic inhibitory effect of clonidine was completely antagonized by yohimbine and slightly by piperoxane and prazosin. Propranolol, mianserin, naloxone and cimetidine did not antagonize the clonidine effect. Clonidine decreased the basal pancreatic secretion in anaesthetized rats and this action was completely reversed by yohimbine. Clonidine inhibited the pancreatic secretion stimulated by 2-deoxyglucose. This effect was reversed by yohimbine, while prazosin had no effect. Clonidine did not inhibit the pancreatic secretion induced by electrical stimulation of the vagus nerves. These results suggest that clonidine inhibition of pancreatic secretion is mediated through alpha 2-adrenergic receptors, and at least in part by a central nervous system mechanism. Yohimbine alone increased basal pancreatic secretion in conscious rats. This suggests that alpha 2-adrenergic receptors might be involved in the physiological nerve tone to the pancreas.