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PubMed1991

Inhibitory effect of ileal oleate on postprandial motility of the upper gut.

To determine the effect of ileal oleate on postprandial gastrointestinal motility, duodenal and paired perfusion-aspiration ileal catheters and bipolar duodenal and jejunal electrodes were surgically implanted in five dogs. The ileum was perfused with either saline or an isotonic oleic acid emulsion at 2 ml/min. A 205-kcal mixed meal containing 120 ml liquid nutrient labeled with 111In-diethylenetriamine pentaacetic acid (DTPA) and solid food labeled with 99mTc was then administered orally. Gastric emptying was assessed by a gamma camera, myoelectric activity was continuously monitored, and duodenal-ileal transit of phenol red was determined over the ensuing 240 min. Ileal oleate reduced duodenal spikeburst frequency by 50% (P less than 0.05) and delayed gastric emptying of liquids and solids. Four hours after ingesting the meal, 62% of solids and 34% of liquids were retained in the stomach during oleic acid perfusion compared with 25 and 4%, respectively, when saline was perfused (P less than 0.05). Duodenal-ileal transit was markedly slowed by ileal perfusion with the oleic acid emulsion (P less than 0.001). Ileal oleate therefore exerted a profound inhibitory effect on proximal gut motility in the early period after ingestion of a mixed-nutrient meal in dogs.

Animals↗
PubMed2003

Excitatory effects of motilin in the hippocampus on gastric motility in rats.

Intestinal motilin is known to stimulate gastrointestinal motility. Recently, it was shown that the motilin gene and the motilin receptor are expressed in various regions of the brain. We studied whether motilin can activate pathways in the rat hippocampus to stimulate gastric motility. Gastric motility was monitored in conscious rats, whereas extracellular electrical activity recordings of the hippocampus were performed on anaesthetized rats to measure the influence of microinjection of motilin and CCK-8 into the hippocampus and into the cerebral ventricles. We found that neurons in the CA3 region of the hippocampus are sensitive to gastric distension, and that injection of motilin into the hippocampus increased the amplitude of gastric contractions by 35.3+/-6.8%, while CCK-8 injection inhibited motility by -27.3+/-6.8%. The hippocampal motilin-induced stimulation of gastric motility (30.6+/-5.5%) was completely abolished by subdiaphragmal vagotomy (-2.8+/-4.4%) but unaffected by the intravenously applied receptor blockers atropine, phentolamine and propranolol. In vivo extracellular recordings of gastric distension-responsive CA3 neurons revealed that intracerebroventricular administration of motilin increased firing while CCK-8 inhibited firing. These opposite effects of motilin and CCK-8 fit with the nature of the actions of these gut-brain peptides on gastric motility. Our findings suggest that the stimulation of gastric motility by motilin administered in the hippocampus reflects the existence of a functional interaction between the hippocampus and a vago-vagus reflex running via a noncholinergic and nonadrenergic efferent pathway.

Action Potentials↗
PubMed2000

A longitudinal study of electrogastrography in normal neonates.

BACKGROUND/PURPOSE: Gastric motility is partly regulated by an inherent electric control activity (ECA). Electrogastrography (EGG) measures gastric ECA through cutaneous electrodes. Little is known about EGG in neonates. A slow wave frequency of 3 cycles per minute (cpm) accounts for 85% to 100% of gastric ECA in normal adults and children. However, the authors have shown previously a lower percentage of 3 cpm activity in neonates. Abnormal EGG patterns (tachygastria and bradygastria) have been described in adults and children with gastric motility disorders. In neonates, especially premature infants, disorders of gastrointestinal motility are common, especially after gastrointestinal operations. It is necessary to characterise normal ECA before the pathophysiology of these disorders can be studied. The aim of this study was to investigate the pattern of ECA in the developing neonate. METHODS: Nine healthy neonates born at 34 weeks' gestation were studied using Synectics EGG sampling at 4 Hz. Each subject underwent 4 hourly EGG recordings at fortnightly intervals from birth until age 8 weeks, and then every 2 months until age 2 years. The paired sample t test (95% Confidence Interval [CI]) was used to compare recordings. RESULTS: Between birth and age 2 years, 3 cpm activity increased from 38% to 57% of recorded time. The mean percentage recorded time of tachygastria decreased from 47% to 35%, and bradygastria decreased from 15% to 8%. Statistically significant differences were seen between birth, 6 months, and 2 years of age. CONCLUSIONS: The pattern of ECA in the normal neonatal stomach differs from that seen in adult studies. Tachygastria and bradygastria are seen more frequently, with fewer periods of 3 cpm. There is an increase in the percentage of 3 cpm activity over time, with statistically significant differences from the ECA pattern at birth first seen at the age of 6 months. The authors suggest that neonatal ECA undergoes a maturation process and that larger longitudinal and normal range studies are required to investigate this phenomenon.

Child, Preschool↗
PubMed2006

Paralytic ileus associated with combined atypical antipsychotic therapy.

First- and second-generation antipsychotics commonly cause mild and sometimes severe gastrointestinal motility depression. We discuss a case of a patient who developed paralytic ileus during his treatment with a combination of second-generation antipsychotics. The patient did not receive other medication that could cause depression of intestinal motility than the above-mentioned combination of antipsychotics and no other etiology could be found for the ileus. Furthermore we discuss the theoretical background of antipsychotics induced gastrointestinal motility depression and we provide the literature review of case reports of this topic.

Antipsychotic Agents↗
PubMed1997

Effects of 3-days' intake of a sustained-release preparation of the nitric oxide donor, isosorbide dinitrate, on oesophageal motility.

BACKGROUND: Nitric oxide plays an important role in gastrointestinal motility. We evaluated the effects of a sustained-release preparation of the nitric oxide donor isosorbide dinitrate on swallow-initiated oesophageal contractions and the lower oesophageal sphincter. METHODS: Twelve healthy men, aged 23-32 years, received, at 1-week intervals and under random double-blind conditions, for 3 days either 20 mg isosorbide dinitrate, 40 mg isosorbide dinitrate or placebo twice daily (b.d.). One hour after a further dose on day 4, oesophageal motility was recorded for 30 min using a multilumen catheter with a Dent sleeve straddling the lower oesophageal sphincter and side-hole openings 0, 3, 6 and 9 cm proximal to the sleeve. Contractile responses to twelve 5-mL water swallows were evaluated. RESULTS: Amplitude, duration, propagation velocity and onset latency of oesophageal contractions were not affected by either dosage of isosorbide dinitrate. Lower oesophageal sphincter resting pressure was significantly lower after 40 mg (15.1 mmHg +/- 1.2 S.E.M.) and 20 mg isosorbide dinitrate b.d. (15.0 +/- 1.0 mmHg) than after placebo (17.9 +/- 1.7 mmHg; P < 0.025). Headache was reported by all subjects on 40 mg isosorbide dinitrate, seven subjects on 20 mg and by one on placebo. CONCLUSIONS: Twenty and 40 mg sustained-release isosorbide dinitrate twice daily had no effect on swallow-initiated oesophageal contractions but decreased lower oesophageal sphincter resting pressure.

Adult↗
PubMed1991

Visceral afferent neuropathy in diabetic gastroparesis.

OBJECTIVE: To determine whether a lack of symptoms in diabetic patients with gastrointestinal motility disorders is associated with visceral afferent neuropathy. RESEARCH DESIGN AND METHODS: We investigated cerebral evoked potentials (EPs) after esophageal stimulation in 10 patients with motor dysfunction of the gastrointestinal tract and in 10 healthy control subjects. All patients had insulin-dependent diabetes mellitus (5 men, 5 women, age range 31-60 yr, diabetes duration 8-36 yr, 10 of 10 with polyneuropathy, 6 of 10 with cardiac autonomic neuropathy). Their esophageal and gastric motor disorders had been diagnosed by scintigraphy, and gastrointestinal stenosis had been excluded by gastroscopy. Only 2 patients had severe symptoms, whereas 6 patients complained of minor discomfort (distension, bloating), and 2 patients were symptom free. RESULTS: EPs were recorded after electrical stimulation of the esophagus (32 cm from the incisors) at intensity just above the perception threshold. All control subjects exhibited regular EPs at 0.1 ms/30 mA stimulation intensity. In 6 diabetic patients, no EPs were detected at 0.1 and 0.3 ms/30 mA, and the perception thresholds were significantly elevated. In 4 patients with normal perception threshold, EPs of regular shape but decreased amplitude were recorded. These patients had mild or severe gastroparetic complaints. CONCLUSIONS: These data show for the first time an association between a lack of symptoms in diabetic gastrointestinal motility disorders and visceral afferent neuropathy.

Adult↗
PubMed1987

Participation of serotonin and substance P in the action of cholecystokinin on colonic motility.

Cholecystokinin (CCK) has a potent stimulatory effect on gastrointestinal motility. The mechanism of CCK-generated contractions in the colon is unknown. We explored the possibility that CCK-mediated contractions in the guinea pig colon occur via a serotonin and/or substance P pathway. In the circular layer, octapeptide of CCK (CCK-8) had no effect under basal conditions, but after treatment with tetrodotoxin the peptide generated dose-dependent contractions (ED50 6 X 10(-8) M). In the longitudinal layer, CCK-8 produced dose-related contractions (ED50 6 X 10(-9) M) blocked by tetrodotoxin and markedly inhibited by the substance P antagonist, Spantide. The effect of substance P was not significantly antagonized by tetrodotoxin but was markedly attenuated by Spantide. Serotonin produced dose-dependent contractions in the longitudinal layer (ED50 4 X 10(-8) M). Desensitization to serotonin antagonized the action of CCK-8 but had no effect on substance P-mediated contractions. Pretreatment with the serotonin antagonist mianserin inhibited CCK-8- but not substance P-generated contractions. In contrast, the stimulatory effect of serotonin was antagonized by Spantide. These studies suggest that in the circular layer of the guinea pig colon CCK-8 has no effect under basal conditions, but after removal of tonic inhibition, the peptide produced a direct stimulatory effect. In contrast, CCK-8 generated contractions in guinea pig colon longitudinal layer, mediated by a pathway involving serotonin and substance P.

Animals↗
PubMed1991

Mechanism of action of peptide YY to inhibit gastric motility.

The pathway by which peptide YY inhibits upper gastrointestinal motility is largely unknown and prompted this investigation. Muscle tension and [3H]acetylcholine release studies were performed on isolated muscle strips and slices obtained from the guinea pig stomach. Peptide YY [0.1-1000 nmol/L; concentration of half-maximal effect (EC50), 6 nmol/L] caused concentration-dependent relaxation of longitudinally oriented muscle strips that was unaffected by hexamethonium but was blocked by atropine and tetrodotoxin, suggesting that the peptide inhibited postganglionic cholinergic neurotransmission. In addition, peptide YY (1 mumol/L) reduced by 42% +/- 6% electrically stimulated muscle contractions that were blocked by atropine and tetrodotoxin, providing additional evidence that the peptide inhibits release of acetylcholine. Next, the effect of peptide YY on potassium-evoked release of [3H]acetylcholine and whether the peptide inhibits cyclic adenosine monophosphate-dependent release of acetylcholine were examined. Peptide YY (1 mumol/L) inhibited KCl (35 mmol/L)-evoked release of [3H]acetylcholine by 58% +/- 6%. The inhibitory action of peptide YY was unaffected by antagonists for dopamine-2, alpha-2, and opiate receptors that are known to mediate presynaptic inhibition. In addition, peptide YY reduced half-maximal forskolin and cholera toxin-evoked release of acetylcholine by 45% +/- 6% and 42% +/- 8%, respectively, suggesting that the peptide can inhibit cyclic adenosine monophosphate-dependent release of acetylcholine. This effect of peptide YY was reversed by pertussis toxin which prevents activation of the inhibitory guanine nucleotide binding protein coupled to adenylate cyclase. In summary, peptide YY inhibited basal and stimulated cholinergic neurotransmission in the guinea pig stomach. In addition, peptide YY antagonized cyclic adenosine monophosphate-mediated release of acetylcholine through a pertussis toxin-sensitive mechanism.

Acetylcholine↗
PubMedDate not supplied

Telemetric small intestinal motility recording in awake rats: a novel approach.

INTRODUCTION: Ideally, gastrointestinal motility recording should be done in freely moving, stress-free animals. However, no such method is currently available for rats. METHODS: Two NiCr electrodes were sutured to the jejunum and connected to an implantable electromyographic (EMG) transmitter in rats. EMG signals were radio-transmitted to a receiver placed at the bottom of the rats' home cages. RESULTS: Fasting and postprandial jejunal EMG signals could be detected by telemetry. Phase III contractions of the MMC were easy to identify visually and occurred at a rate of about 4.8 per hour. Feeding disrupted the phasic contraction pattern 15 min after the start of food intake and lasted for 2 h. The motility index (MI, area under the curve) was calculated and increased postprandially. CONCLUSION: Telemetric transmission of rat gastrointestinal EMG signals is feasible and results are comparable to those given in the literature.

Animals↗
PubMed2006

Contractile effects of ghrelin-related peptides on the chicken gastrointestinal tract in vitro.

Ghrelin is an endogenous ligand for growth hormone secretagogue receptor (GHS-R), and it stimulates growth hormone (GH) release, food intake and gastrointestinal motility in mammals. Ghrelin has also been identified in the chicken, but this peptide inhibits food intake in the chicken. We examined the effects of ghrelin and related peptides on contractility of the isolated chicken gastrointestinal tract in vitro. Among ghrelin-related peptides examined (1 microM of rat ghrelin, human ghrelin, chicken ghrelin and growth hormone releasing peptide-6 (GHRP-6)), only chicken ghrelin was effective on contraction of the chicken gastrointestinal tract. Des-acyl chicken ghrelin was ineffective, suggesting that octanoylation at Ser3 residue of chicken ghrelin was essential for inducing the contraction. Amplitude of chicken ghrelin-induced contraction was region-specific: highest in the crop and colon, moderate in the esophagus and proventriculus, and weak in the small intestine. The contractile response to chicken ghrelin in the crop was not affected by tetrodotoxin (TTX), but that in the proventriculus was decreased by TTX and atropine to the same extents. D-Lys3-GHRP-6 (a GHS-R antagonist) caused a transient contraction and inhibited the effect of chicken ghrelin without affecting the high-K+-induced contraction. Chicken ghrelin potentiated electrical field stimulation-induced cholinergic contraction without affecting the responsiveness to bath-applied carbachol in the proventriculus. The location of GHS-R differs in the crop (smooth muscle) and proventriculus (smooth muscle and enteric neurons). These results indicate that ghrelin has contractile activity on gastrointestinal tract in the chicken in vitro, and the effect was region-specific. The action would be mediated through the GHS-R, which is highly sensitive to chicken ghrelin.

Animals↗
PubMed2005

Sulphonylurea receptors differently modulate ICC pacemaker Ca2+ activity and smooth muscle contractility.

Appropriate gastrointestinal motility is essential to properly control the body energy level. Intracellular Ca2+ ([Ca2+]i) oscillations in interstitial cells of Cajal (ICCs; identified with c-Kit immunoreactivity) are considered to be the primary mechanism for the pacemaker activity in gastrointestinal motility. In the present study, RT-PCR examinations revealed predominant expression of the type 1 isoform of sulphonylurea receptors (SUR1) in ICCs of the mouse ileum, but expression of SUR2 was predominant in smooth muscle. In cell clusters prepared from the same tissue, smooth muscle contractility and pacemaker [Ca2+]i activity in ICCs were found to be differentially modulated by K(ATP) channel openers and sulphonylurea compounds, in accordance with the expression of SUR isoforms. 1 microM cromakalim nearly fully suppressed the mechanical activity in smooth muscle, whereas ICC pacemaker [Ca2+]i oscillations persisted. Greater concentrations (approximately 10 microM) of cromakalim attenuated pacemaker [Ca2+]i oscillations. This effect was not reversed by changing the reversal potential of K+, but was prevented by glibenclamide. Diazoxide at 30 muM terminated ICC pacemaker [Ca2+]i oscillations, but again treatment with high extracellular K+ did not restore them. These results suggest that SUR can modulate pacemaker [Ca2+]i oscillations via voltage-independent mechanism(s), and also that intestinal pacemaking and glucose control are closely associated with SUR.

ATP-Binding Cassette Transporters↗
PubMed2004

Electrodynamic smooth muscle sphincter: development and biomechanical evaluation of a novel porcine artificial smooth muscle sphincter in a new in vitro stoma simulator.

AIM: Many authors have suggested that the activity of the enteric inhibitory nerves is important in regulating normal gastrointestinal motility and inducing smooth muscle relaxation. Hitherto, no experimental or clinical models exist that transfer these physiological aspects to creating an autologous artificial sphincter for the treatment of major incontinence. Therefore, this study was performed to determine the contractile and relaxant capacity of gastrointestinal muscle types and to investigate the efficiency of a novel smooth muscle sphincter, based on the non-adrenergic, non-cholinergic (NANC) receptive relaxation under electrical field stimulation (EFS). METHODS: For the first step, the isometric tension from isolated circular porcine fundus and colon muscle strips was recorded during pharmacological stimulation (TTX, L-NNA and atropine) and EFS. As a result, a continent electrodynamic smooth muscle sphincter (ESMS) was created by wrapping a fundus muscle flap around an isolated segment of porcine distal colon. The EFS of the free nerve fibers of the flap was realized using a circular platinum wire electrode. Parameters such as threshold of continence, intra/preluminal pressure and fluid passage were analyzed in a newly designed in vitro stoma simulator. RESULTS: Electrical field stimulation produced a maximal and voltage-dependent fundus relaxation to --12.4 mN/mm(2) (frequency of 40 Hz, pulse duration, train duration and voltage of 5 ms, 1 s and 60 mA respectively), which were abolished by N-nitro-L -arginine (L-NNA; 10(-4) M) in a dose-dependent manner, confirming that relaxant responses were mediated by NANC nerves. The results of eight ESMS showed that circular electrical stimulation of the muscle flap caused muscle relaxation with a concomitant and effective reduction in the occlusion pressure. CONCLUSION: The NANC-induced relaxation mechanism of porcine fundus preparations could be transferred to an efficient smooth muscle sphincter with a high threshold of continence and electrically controlled defecation.

Anal Canal↗
PubMed1992

The patterns of motility are maintained in the human small intestine throughout the process of aging.

Intestinal disorders suggesting impaired gastrointestinal motility due to aging have been reported, but the influence of advanced age on the patterns of motility in the human small intestine is unknown. The present prospective study describes these patterns of motility in 15 healthy old subjects with a median of 84 years (range, 81-91 years). Nineteen healthy young adults served as controls. Ambulatory manometry was performed at home, with two sensors located in the proximal small intestine. Postprandial motility was induced by a standardized meal at 1800 h, and fasting motility was recorded during the subsequent night. Migrating motor complex (MMC) data were analysed by means of an expanded variance component model. Recurrent MMCs were identified during fasting in all individuals, with similar periodicity in old and young adults (p = 0.4). The propagation velocity of phase III of MMC was slower in the old subjects (6.5 +/- 0.8 cm/min versus 10.8 +/- 1.2 cm/min; p less than 0.01). Duration of postprandial motility was preserved, as were the amplitude and frequency of contractions during phase III and the postprandial state. Propagated clustered contractions were more frequently present in old subjects both after a meal (67% versus 11%; p less than 0.01) and during fasting (p less than 0.01); otherwise the patterns of motility are maintained in the human small intestine throughout the process of aging.

Aged↗
PubMed2002

Single millimeter wave treatment does not impair gastrointestinal transit in mice.

Millimeter wave treatment (MWT) is based on those biological effects that develop following skin exposure to low power electromagnetic waves. This method of treatment is in wide clinical use in several Eastern European countries for treatment of a variety of conditions, including pain syndromes. However, most treatment modes of MWT were developed empirically, and certain indications and contraindications for the use of MWT remain to be established. In our previous blind experiments we have shown that the hypoalgesic effect of MWT may be quantitatively evaluated, and most probably mediated by the neural system in general, and the system of endogenous opioids in particular. Taking in consideration a well-known ability of opioids to cause gastrointestinal disturbances, which could limit clinical application of MWT, the main aim of the present study was to investigate whether a single MWT, that can produce opioid-related hypoalgesia, may also retard gut transit and colorectal passage in mice. The charcoal meal test was used to quantitatively evaluate upper gastrointestinal transit, and the glass bead test was employed to examine colonic propulsion in mice. MWT was applied to the nose area of mice. The MWT characteristics were: frequency = 61.22 GHz; incident power density = 15 mW/cm(2); and duration = 15 min. The results obtained have shown that MWT does not significantly change small intestinal or colonic transit in mice, and thus suppression of gastrointestinal motility should not be a setback in the clinical use of MWT.

Analgesia↗
PubMed2001

Evaluation of methanolic extract of Ficus platyphylla on gastrointestinal activity.

Methanolic extract of Ficus platyphylla was tested on isolated rabbit jejunum, rat duodenum and gastrointestinal motility in mice. The extract showed a biphasic effect on isolated smooth muscle. Lower concentration of extract caused contraction, while higher concentrations produced relaxation. The contractile phase was attenuated by atropine, while relaxant phase attenuated histamine induced contraction of guinea pig ileum. The extract also exhibited a dose-dependent inhibition of gastrointestinal motility. Acute toxicity test in mice established LD50 value (i.p.) of the extract to be 2000 mg/kg. Preliminary phytochemical screening of the extract gave positive test for flavonoids, tannins and saponins.

Animals↗
PubMed1993

Effects of cholinoceptor and 5-hydroxytryptamine3 receptor antagonism on erythromycin-induced canine intestinal motility disruption and emesis.

1. Erythromycin administration is associated with gastrointestinal problems, disturbed gastrointestinal motility and emesis. This study in the dog investigates the underlying mechanisms. 2. Intestinal myoelectrical activity and the occurrence and latency of emesis were recorded in eight conscious dogs. All drugs were administered intravenously. 3. Erythromycin (7 mg kg-1) increased contractions of the proximal small intestine, and caused emesis in all fasted dogs and in 5 dogs after food. Atropine (50 mg kg-1 min-1) and hexamethonium (10 mg kg-1 h-1) partially inhibited the GI motility effects but did not significantly reduce emesis. 4. Metoclopramide at a high dose (2 mg kg-1 h-1) reduced the incidence of emesis in the presence of increased intestinal motility, but a low dose (150 micrograms kg-1 h-1) was ineffective. 5. A 5-hydroxytryptamine3 (5-HT3) receptor antagonist, MDL 72222 (1 mg kg-1), reduced emesis when given alone and combined with metoclopramide (low dose). The 5-HT4 receptor agonist BRL24924 (Renzapride, 1 mg kg-1) had no effect on emesis either alone in combination with metoclopramide. 6. In conclusion, erythromycin-induced GI motility disturbances and emesis are not causally related. Whereas the increase in intestinal smooth muscle activity is possibly cholinergically mediated, emesis occurs at least in part via a 5-hydroxytryptaminergic mechanism, but does not involve the dopamine system.

Animals↗
PubMed2005

[Effects of perioperative administration of Rhubarb on acute inflammatory response in patients with gastric cancer].

OBJECTIVE: To observe the effect of perioperative administration of rhubarb on the acute inflammatory response in patients with gastric cancer. METHODS: In this prospective, single-blinded, controlled clinical trial, thirty-one patients with gastric cancer operatively treated were randomly divided into two groups, with 14 patients in control group and 17 in study group. Patients in both groups were given an isocaloric and isonitrogenous enteral diet. The enteral diet was started 36 hours after operation, and continued for 6 days. Patients in the study group were fed with rhubarb before operation, and at 1 day and 2 days after operation. Indexes of acute inflammatory response such as serum C-reactive protein (CRP), interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-alpha), and indexes of nutritional status such as serum albumin (ALB), prealbumin (PA) and transferrin (TRF) were measured before operation, and at 1 day, 3 and 7 days after operation. RESULTS: Patients in both groups had acute inflammatory response, and the indexes of nutritional status decreased after operation.IL-6, CRP and TNF-alpha tested at 3 and 7 days after operation were lower in the study group as compared with those in the control group, and the recovery time of gastrointestinal motility such as borborygmus, gas elimination and defecation was shorter in the study group as compared with that in the control group. The indexes of nutritional status showed no significant differences between two groups after operation. CONCLUSION: Rhubarb can positively modulate the acute inflammatory response, promote the recovery of postoperative gastrointestinal motility, and benefit enteral nutrition support in patients who have undergone major operations for gastric cancer.

Adult↗
PubMedDate not supplied

A simple method to investigate the inhibitory effects of drugs on gastric emptying in the mouse in vivo.

INTRODUCTION: The aim was to develop a simple method to study modification of gastric motility in the mouse in vivo. METHODS: Mice were fed a hydrated diet in which the fluid content of standard laboratory chow was increased by adding water. Gastric emptying was assessed at specified times following a 1-h treatment period with orally administered pharmacological agents. RESULTS: We demonstrated consistent and progressive gastric emptying over a 4-h period, stomach content being decreased from 7.52+/-0.90 at time zero to 2.80+/-0.25 mg/g body weight after 4 h. Results demonstrated typical effects of inhibitory agents (atropine and morphine) and showed inhibitory effects of three potassium channel opening agents, pinacidil, cromakalim, and SDZ PCO400: the residue remaining in the stomach was increased by 3.66+/-0.84, 6.56+/-1.35, and 5.68+/-1.33 mg/g body weight respectively 1 h after treatment with 10 mg/kg of these agents, compared to vehicle controls. DISCUSSION: The inhibitory activity observed correlated well with previous studies on the effects of potassium channel opening agents on mouse gastrointestinal motility in vivo and in vitro. The present model may thus be of value in the pharmacological investigation of gastrointestinal motility owing to cost and convenience advantages, together with the possibility of its application to studies using transgenic animals.

Administration, Oral↗