Guey-Hwa Yeh

Influence of blood glucose levels on rat liquid gastric emptying

The glycemic influence on liquid gastric emptying in rats was studied. Diabetic hyperglycemia was induced by streptozotocin intravenous injection seven days before the motility experiment. Some streptozotocin-treated rats further received a daily insulin injection (2.5 or 10 IU/kg). Immediate hyperglycemia was induced in a separate group of rats by continuous intravenous glucose infusion (44 or 88 mg/kg/min) 10 min before the experiment. Rats were killed 15 min after radiochromium feeding; then the radioactivity of stomach and small intestine were counted to obtain the gastric emptying value. Emptying in diabetic rats was delayed compared with controls (mean±se: 40.9±2.6% vs. 54.2±2.8%,P<0.01). Low-dose insulin treatment reversed the impairment, while high-dose treatment even enhanced emptying. Immediate hyperglycemia induced with two glucose infusions also inhibited gastric emptying. Present results indicate that hyperglycemia elicited with any hyperglycemic model is at least one of the important mechanisms to delay liquid gastric emptying.

Disturbed Small Intestinal Motility in the Late Rat Pregnancy

We investigated whether various periods of pregnancy might disturb rat gastrointestinal motility. When the proestrus of female rats occurred, they were housed with male rats. Motility studies were conducted on day 7 (first period), day 14 (second) and day 21 (third) of pregnancy, respectively. After the orogastric feeding of radiochromium marker, rats were sacrificed 15 min later. Gastric emptyings of pregnant rats measured at various periods did not differ from the nonpregnant diestrus controls. The geometric center represented intestinal transits in the first, second and third periods of pregnancy and controls were (mean ±SEM) 4.54 ± 0.25, 4.47 ± 0.17, 3.61 ± 0.27 and 4.98 ± 0.13, respectively (p < 0.01) while their plasma progesterone levels were 15.6 ± 2.6, 18 ± 1.4, 7.1 ± 0.5 and 8.6 ± 0.4 ng/ml, respectively (p < 0.01). This shows that late pregnancy inhibits small intestinal transit, whereas gastric emptying remains unchanged. Altered progesterone during pregnancy is not a main mediator to disturb intestinal transit.

Rat gastrointestinal motor responses mediated via activation of neurokinin receptors

Natural neurokinins (NK) and their specific receptor agonists, including substance P (SP), neurokinin A (NKA), neurokinin B (NKB), septide, [NIe 10 ]‐NKA4–10 and senktide, were used to assess whether they could activate established NK receptors in rat gastrointestinal tract and central nervous system to alter gastric emptying or intestinal transit. Fasting rats were intubated with an orogastric catheter to feed them liquid radiochromium. Neurokinins and analogues (at 10−10, 10−9, 10−8 and 10−7 mol/kg) and vehicle (saline +0.1% bovine serum albumin) were injected via an intraperitoneal route. Rats were killed 15 min later and the whole gut was removed. The radioactivity of the stomach and 10 equally divided small intestinal segments was counted to determine gastric emptying and the geometric centre of intestinal transit. Septide treatment at 10−8 and 10−7 mol/kg markedly delayed gastric emptying. All doses of NKA inhibited gastric emptying. However, other peptides did not influence gastric emptying. Both septide and NKB treatment at 10−8 and 10−7 mol/kg enhanced intestinal transit. Substance P or senktide treatment (10−7 mol/kg) also enhanced intestinal transit. Stasis of remaining radioactivity in the proximal intestine was found following SP, septide, NKA and NKB treatment, whereas accelerated transit in the distal intestine was induced following NKA, NKB and senktide treatment. In conclusion, the in vivo study of NK and their specific agonists manifests a selective influence of these compounds on rat gastrointestinal tract. This selective activation of stomach NK1 and NK2 receptors delays gastric emptying, whereas activation of intestinal NK1 and NK3 receptors enhances intestinal transit.

Comparison of Two Orogastric Feeding Markers for Measuring Gastrointestinal Motor Functions in Rats

Rat gastrointestinal (GI) transit parameters measured with charcoal and radiochromium were compared. Animals were fed with a calorie-free liquid test meal which contained 10% charcoal and radiochromium (0.5 microCi ml-1) via a transiently placed orogastric catheter. The rats were sacrificed at 1, 5, 15, 30, 60 and 120 min, respectively, since feeding. Various motor parameters were measured. Charcoal transit ratio, gastric emptying and geometric center were time dependent. Charcoal transit ratio occasionally showed a positive correlation with gastric emptying in the very late experimental periods. Concerning the correlation of charcoal transit ratio and geometric center, negative and positive correlations were seen in the very early and late periods, respectively. We conclude that the rat charcoal transit ratio has limited value to replace the GI transit parameters determined by feeding radiochromium.

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.

Influence of pregnancy and uterine weight on rat gastrointestinal transit

Orogastric feeding of a charcoal meal to rats was employed to measure whether the various stages of pregnancy could influence gastrointestinal transit. The oestrous cycle of female Sprague‐Dawley rats was checked daily. If pro‐oestrus occurred, the first day of pregnancy was defined to be on the next day after the copulation. Gastrointestinal transit studies were conducted on day 7 (first trimester), day 14 (second) and day 21 (third), respectively. The rats were killed 15 min after the successful feeding of a calorie‐free, charcoal‐containing test meal via a transiently placed orogastric catheter. Gastrointestinal transit was defined as the per cent of charcoal transit divided by the total length of the small intestine. These results were compared with the data obtained from non‐pregnant female rats. Mean percentages of transit for the first, second and third trimester, and for controls were 42.8 ± 1.9, 45.3 ± 4.1, 35.7 ± 1.7 and 42.6 ± 1.4%, respectively (mean ± s.e.). Late pregnancy elicited a marked inhibition of transit (P < 0.01). A significant negative correlation between transit and uterine weight of all pregnant rats was seen (r= ‐0.50, P < 0.05). The present study indicates that inhibited gastrointestinal transit occurs in the late pregnant rat.

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.