Ming-Luen Doong

A novel simultaneous measurement method to assess the influence of intracerebroventricular obestatin on colonic motility and secretion in conscious rats

Obestatin, a novel putative 23-amino acid peptide, is derived from mammalian preproghrelin gene via a bioinformatics approach. Although obestatin regulates thirst, sleep, memory, anxiety, activates cortical neurons in the brain and stimulate proliferation of retinal pigment epithelial cells, there is no study to explore its central impacts on the lower gut motility and secretion. We investigated the influence of intracerebroventricular (ICV) injection of obestatin on rat colonic motor and secretory functions. Colonic transit time, fecal pellet output and fecal content were assessed in freely fed, conscious rats, which were implanted with ICV and colonic catheters chronically. Human/rat corticotropin-releasing factor (h/rCRF) was applied as a stimulatory inducer of colonic motility and secretion. ICV injection of obestatin (0.1, 0.3, 1.0 nmol/rat) did not modify the colonic transit time, whereas ICV injection of h/rCRF (0.3 nmol/rat) significantly shortened colonic transit time. ICV obestatin in any dose we tested did not affect the fecal pellet output, frequency of watery diarrhea, total fecal weight, fecal dried solid weight, or fecal fluid weight in the first hour post-injection, either. In contrast, ICV injection of h/rCRF effectively stimulated fecal pellet output, as well as increased total fecal weight, fecal dried solid weight and fecal fluid weight during the first hour post-injection, compared to ICV saline controls. In conclusion, using our novel simultaneous measurement method, acutely central administration of obestatin exhibits no influence on colonic motility and secretion in conscious rats.

Vasoactive intestinal polypeptide appears to be one of the mediators in misoprostol‐enhanced small intestinal transit in rats

Abstract Background and Aims: Prostaglandin analogs have the pharmacologic effect of speeding up small intestinal transit (SIT). It remains unknown whether some gut peptides also mediate this enhancement. We studied the effect of misoprostol on rat SIT and looked at the role of vasoactive intestinal polypeptide (VIP) release during its action.

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 μg/kg. Another group of rats received misoprostol intraperitonally at doses of 10, 50, 250, and 500 μg/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 μg/kg did not influence emptying, whereas other doses delayed emptying (p < 0.01). Except the 10- μg/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.

Intracerebroventricular Ghrelin Enhances Non-Nutrient Semiliquid Gastric Emptying in Fasted Conscious Rats

Background and Aims: Although peripheral and central impacts of ghrelin on food intake as well as the peripheral influence of ghrelin on gut motility are well known, the central effect of acyl ghrelin on gastric motility in rats remains uninvestigated. We aimed, first, to establish a stable, conscious rat model to measure non-nutrient, semiliquid gastric emptying, and second, to investigate the effect of intracerebroventricular (ICV) injection of acyl ghrelin on gastric emptying. Methods: We investigated the temporal effects of charcoal, non-nutrient, semiliquid gastric emptying in 16-h food-deprived, conscious rats chronically implanted with ICV cannula. Then, we studied the dose-response effect of ICV acyl ghrelin on charcoal, non-nutrient, semiliquid gastric emptying in fasted conscious rats. Results: Stable, temporal effects of charcoal, non-nutrient, semiliquid gastric emptying in chronically ICVcannulated, conscious rats were created first, and 30-min non-nutrient, semiliquid gastric emptying was selected among them for the subsequent experiments. ICV-injected ghrelin (0.1, 0.3 and 1.0 nmol/rat) enhanced 30-min nonnutrient, semiliquid gastric emptying in fasted conscious rats. Conclusions: We established a reliable, in vivo animal model to measure the effects of peptides or chemicals in the forebrain on gastric motility. ICV administration of ghrelin effectively enhances 30-min non-nutrient, semiliquid gastric emptying in fasted conscious rats. The optimal doses of ghrelin at 0.1 and 0.3 nmol on gastric emptying could be chosen in the future to study the interactions between ghrelin and other gut motility inhibitory peptides, such as corticotropin-releasing factor peptide families and cholecystokinin.

Interaction of carbohydrate metabolism and rat liquid gastric emptying in sustained running

Background:  Moderate to severe running usually leads to gastrointestinal dysmotility and critical energy exhaustion. It is unknown whether the carbohydrate metabolism of runners can influence gastric emptying (GE). Using a running rat model, the present study explored the impact of exercise/carbohydrate metabolism on liquid GE.

Gastric inhibitory polypeptide and gastric acid secretion in pregnant rats

The effects of pregnancy on the basal and pentagastrin-stimulated gastric acid secretion and the level of plasma gastric inhibitory polypeptide (GIP) in rats were studied on pentobarbital-anaesthetized non-pregnant rats and rats in the 1st, 2nd, or 3rd week of gestation. Acid output was determined by titration of the gastric perfusate. Basal secretion was collected for 45 min before a 30 min infusion of pentagastrin (8 micrograms/ml/300 g body weight). Concentration of plasma GIP was measured by a radioimmunoassay (RIA). The immunoreactivity of GIP-like substance in the extract of the rat placenta collected from the rat at day 21 of gestation was examined by RIA. The biological activity of GIP-like substance in the rat placenta extract was tested by the reduction of pentagastrin-stimulated gastric acid secretion in male rats. The basal level of gastric secretion was higher in late pregnancy as compared with the non-pregnant rats. Pentagastrin induced a greater increase of gastric acid secretion in early but not late pregnant rats as compared with the non-pregnant animals. The basal and post-pentagastrin level of plasma GIP was higher in rats in late pregnancy. Both immunoreactivity and biological activity of GIP exist in the rat placenta extract. These results suggest that the normalization of gastric acid secretion in late pregnant rats is at least in part due to the production of GIP-like substance from placenta.

Human chorionic gonadotropin regulates gastric emptying in ovariectomized rats

Prolongation of gastrointestinal transit resulting in nausea and vomiting in pregnancy (NVP) is the most common phenomenon during the first trimester of pregnancy. Increased human chorionic gonadotropin (hCG) concentration during the first trimester is the most likely cause of NVP. The aim of this study was to investigate the effect of hCG on gastrointestinal transit and plasma concentrations of cholecystokinin (CCK) in ovariectomized (Ovx) rats. I.p. injection of hCG was used to evaluate the dose effect of hCG on gastrointestinal transit in Ovx rats. The CCK antagonist lorglumide was used to clarify the role of CCK in regulating gastrointestinal transit. Gastrointestinal transit was assessed 15 min after intragastric gavage of a mixture of 10% charcoal and Na(2)(51)CrO(4) (0.5 μCi/ml). After i.p. administration of hCG, gastric emptying was inhibited in Ovx rats, but intestinal transit was not affected. Plasma CCK concentrations were increased in a dose-dependent manner after hCG treatment, and gastric emptying showed a significant negative correlation with CCK concentrations (P=0.01, r(2)=-0.5104). Peripheral administration (i.p.) of lorglumide, a selective CCK(1) receptor antagonist, attenuated the hCG-induced inhibition of gastric emptying in Ovx rats, whereas central administration via the i.c.v. route did not. hCG treatment of Ovx rats inhibits gastric emptying in a dose-dependent manner via a peripheral mechanism of CCK hypersecretion and activation of CCK(1) receptors.

Queckenstedt's Test Affects More than Jugular Venous Congestion in Rat

Jugular venous compression by the Queckenstedts test (Q-test) increases the intracranial pressure, but the effects of isolated jugular venous congestion are not well known. Intraventricular pressure (IVP) was compared during direct obstruction of the common jugular veins (bilateral CJV clipping) and during external compression of bilateral CJV flows (Q-test) in a rat model. Intracerebroventricular catheters were inserted into the right lateral ventricle of nine male Sprague-Dawley rats (371.1±44.8 g, 82.2±12.0 days old). The initial mean IVP, arterial pressure (MAP), and pulse rate were 2.8±1.3 mmHg, 88.8±12.7 mmHg, and 348.3±69.1 beats/min, respectively. The mean IVP increment and MAP decrement were 6.5±2.5 and 13.5±5.7 mmHg, respectively, during the Q-test, compared to 2.3±1.5 and 7.3±3.8 mmHg, respectively, during bilateral CJV clipping (all p = 0.008). The IVP increment and MAP decrement were greater during the Q-test than during bilateral CJV clipping (p = 0.008 and p = 0.038). Although the Q-test and bilateral CJV clipping showed similar effects, the response with the Q-test was greater. Thus, the Q-test appears to obstruct other collateral cerebral veins in addition to bilateral CJV flows. Since this model revealed significant differences between the manual Q-test and bilateral CJV clipping, the finding should be taken into account in future studies on the Q-test in SD rats.

Acid-inhibitory potency of ranitidine in diabetic rats

The pharmacological potency of ranitidine to inhibit pentagastrin-stimulated gastric acid outputs was studied in early diabetic rats. Diabetes was induced by intravenous injection of streptozotocin 4 days before the acid study. The gastric acid output was measured every 5 min by automatic titration of collected gastric perfusates. Basal acid was collected for 45 min before a 90-min infusion of pentagastrin. Thirty minutes after onset of the pentagastrin infusion, the rats received intravenous bolus injections of ranitidine at doses of 0.03, 0.3, or 3 mg/kg. Diabetes induction obviously increased the acid-secretory ability during the pentagastrin stimulation period. Ranitidine given at the low dose to diabetic rats showed no apparent inhibitory potency (mean ± SE 106 ± 3.4 vs. 63.9 ± 3.3%, p < 0.01) with shorter duration (21.3 ± 5.4 vs. 44.4 ± 7.9 min, p < 0.05) of inhibited acid output as compared with controls. The median dose of ranitidine treatment produced less effect of an acid-inhibitory potency in diabetic rats (p < 0.05). Among the rats which received the high dose of ranitidine, the inhibitory action on the acid secretion remained diminished in diabetic rats (39.3 ± 2.1 vs. 55.1 ± 4.2%, p < 0.05). In conclusion, short-term diabetes induction in rats enhances their stimulatory acid output ability, but attenuates the pharmacologically inhibitory action of ranitidine on the stimulated acid output.

Distal stomach appears essential in the regulation of gastrointestinal transit.

Abstract: Stomach and small bowel both influence gastrointestinal motility. We studied which portion of the stomach was essential for the regulation of gastrointestinal movement and determined the role of vasoactive intestinal polypeptide in this regulation. The study subjects consisted of 45 controls, 46 patients after subtotal gastrectomy, and 13 patients after total gastrectomy for stomach cancer. Orocecal transit time was measured, using the hydrogen breath test, to represent gastrointestinal movement, while plasma vasoactive intestinal polypeptide level was simultaneously assessed. The orocecal transit times in the study groups were (means ± SD) 91.1 ± 45.0, 57.1 ± 34.3, and 60.8 ± 34.8 min, respectively (P < 0.01). In the subtotal gastrectomy patients, age showed a negative correlation with orocecal transit time (r = −0.388; P < 0.01). In the total gastrectomy patients, no particular demographic factor influenced orocecal transit. Plasma vasoactive intestinal polypeptide levels in the three groups were 20.7 ± 10.8, 22.7 ± 10.9, and 20.6 ± 9.1 pg/ml, respectively (NS). We conclude that both types of gastrectomies enhanced gastrointestinal movement, showing a similar effect, and that the distal stomach plus pylorus are most likely to exert an important inhibitory mechanism in the regulation of this movement. Vasoactive intestinal polypeptide is not a major peptide mediating this regulation.