Human Gastrointestinal Motility Research Articles

Motilin fluctuations in healthy volunteers determined by liquid chromatography mass spectrometry.

Motilin is a hormone secreted by specialised enteroendocrine cells in the small intestine, and is known to modulate gastrointestinal motility in humans, regulating the migratory motor complex. It is understudied at least in part due to the lack of commercially available immunoassays. A multiplexed liquid chromatography mass spectrometry (LC-MS/MS) method was optimised to measure motilin, insulin, C-peptide, GIP (1-42) and GIP (3-42). Corresponding active ghrelin concentrations were determined by immunoassay. Ten healthy volunteers with no prior history of gastroenterological or endocrine condition attended after overnight fast and had blood samples taken every 15 minutes for 4 hours whilst continuing to fast, and then further sampling for 2 hours following a liquid mixed meal. Hunger scores were taken at each time point using a visual analogue scale. Normal bowel habit was confirmed by 1 week stool diary. Motilin levels fluctuated in the fasting state with an average period between peaks of 109.5 mins (SD:30.0), but with no evidence of a relationship with either ghrelin levels or hunger scores. The mixed meal interrupted cyclical motilin fluctuations, increased concentrations of motilin, insulin, C-peptide, GIP(1-42) and GIP(3-42), and suppressed ghrelin levels. This study highlights the utility of LC-MS/MS for parallel measurement of motilin alongside other peptide hormones, and supports previous reports of the cyclical nature of motilin levels in the fasting state and interruption with feeding. This analytical method has utility for further clinical studies into motilin and gut hormone physiology in human volunteers.

Development and analysis of a multi-module peristaltic simulator for gastrointestinal research

Many existing in vitro digestion systems do not accurately represent the peristaltic contractions of the gastrointestinal system; most of the systems that have physiologically-relevant peristaltic contractions have low throughput and can only test one sample at a time. A device has been developed that provides simulated peristaltic contractions for up to 12 digestion modules simultaneously using rollers of varying width to modulate the dynamics of the peristaltic motion. The force applied to a simulated food bolus varied from 2.61 ± 0.03 N to 4.51 ± 0.16 N (p < 0.05) depending on roller width. Video analysis showed that the degree of occlusion of the digestion module varied from 72.1 ± 0.4% to 84.6 ± 1.2% (p < 0.05). A multiphysics, computational fluid dynamics model was created to understand the fluid flow. The fluid flow was also examined experimentally using video analysis of tracer particles. The model-predicted maximum fluid velocity in the peristaltic simulator incorporating the thin rollers was 0.016 m/s, and the corresponding value measured using tracer particles was 0.015 m/s. The occlusion, pressure, and fluid velocity in the new peristaltic simulator fell within physiologically representative ranges. Although no in vitro device perfectly recreates the conditions of the gastrointestinal system, this novel device is a flexible platform for future gastrointestinal research and could allow for high-throughput screening of food materials for health-promoting properties under conditions representative of human gastrointestinal motility.

Simulating human gastrointestinal motility in dynamic in vitro models.

The application of dynamic in vitro gastrointestinal (GI) models has grown in popularity to understand the impact of food structure and composition on human health. Given that GI motility is integral to digestion and absorption, a predictive in vitro model should faithfully replicate the motility patterns and motor functions in vivo. In this review, typical characteristics of gastric and small intestinal motility in humans as well as the biomechanical and hydrodynamic events pertinent to gut motility are summarized. The simulation of GI motility in the presently existing dynamic in vitro models is discussed from an engineering perspective and categorized into hydraulic, piston/probe-driven, roller-driven, pneumatic, and other systems. Each system and its representative models are evaluated in terms of their motility patterns, the key hydrodynamic characteristics concerning gut motility, their performance in simulating the key physiological events, and their ability to establish in vitro-in vivo correlations. Practical Application: The review paper provided useful information in the design of dynamic GI models and the simulation of human gastric and small intestinal motility which are important for understanding food and health.

Gastrointestinal Motility and Functional Disorders

Gastrointestinal (GI) motility disorders represent diseases characterized by abnormal, predominantly impaired, sometimes exaggerated, movement of contents through the GI tract due to neuromuscular dysfunctions in the absence of mucosal disease and mechanical causes of impaired passage. By contrast, functional GI disorders represent illnesses, defined only by GI symptoms, which occur in the absence of mucosal or structural abnormality or of known biochemical or metabolic disorders. The first section of this chapter discusses the enteric and extrinsic neural regulation of GI sensorimotor functions and normal GI motility in humans. Disorders such as gastroparesis (including diabetic gastroparesis, idiopathic gastroparesis, and postsurgical gastroparesis), dumping syndrome, intestinal pseudo-obstruction, small intestinal bacterial overgrowth, megacolon (including Hirschsprung disease, toxic megacolon, and colonic pseudo-obstruction), chronic constipation (including defecatory disorders, normal transit constipation, and slow transit constipation), functional dyspepsia, functional diarrhea and irritable bowel syndrome, and fecal incontinence are then discussed in depth. Tables present a comparison of GI motility and functional disorders, the causes of gastroparesis, the etiology of intestinal pseudo-obstruction and fecal incontinence, common medical conditions and medications associated with constipation, and the symptom severity scale in fecal incontinence. Illustrations, graphs, magnetic resonance images, and algorithms are provided. This chapter contains 10 highly rendered figures, 6 tables, 92 references, and 5 MCQs.

Gastrointestinal Motility and Functional Disorders

Gastrointestinal (GI) motility disorders represent diseases characterized by abnormal, predominantly impaired, sometimes exaggerated, movement of contents through the GI tract due to neuromuscular dysfunctions in the absence of mucosal disease and mechanical causes of impaired passage. By contrast, functional GI disorders represent illnesses, defined only by GI symptoms, which occur in the absence of mucosal or structural abnormality or of known biochemical or metabolic disorders. The first section of this chapter discusses the enteric and extrinsic neural regulation of GI sensorimotor functions and normal GI motility in humans. Disorders such as gastroparesis (including diabetic gastroparesis, idiopathic gastroparesis, and postsurgical gastroparesis), dumping syndrome, intestinal pseudo-obstruction, small intestinal bacterial overgrowth, megacolon (including Hirschsprung disease, toxic megacolon, and colonic pseudo-obstruction), chronic constipation (including defecatory disorders, normal transit constipation, and slow transit constipation), functional dyspepsia, functional diarrhea and irritable bowel syndrome, and fecal incontinence are then discussed in depth. Tables present a comparison of GI motility and functional disorders, the causes of gastroparesis, the etiology of intestinal pseudo-obstruction and fecal incontinence, common medical conditions and medications associated with constipation, and the symptom severity scale in fecal incontinence. Illustrations, graphs, magnetic resonance images, and algorithms are provided. This chapter contains 10 highly rendered figures, 6 tables, 92 references, and 5 MCQs.

Gastrointestinal Motility and Functional Disorders

Gastrointestinal (GI) motility disorders represent diseases characterized by abnormal, predominantly impaired, sometimes exaggerated, movement of contents through the GI tract due to neuromuscular dysfunctions in the absence of mucosal disease and mechanical causes of impaired passage. By contrast, functional GI disorders represent illnesses, defined only by GI symptoms, which occur in the absence of mucosal or structural abnormality or of known biochemical or metabolic disorders. The first section of this chapter discusses the enteric and extrinsic neural regulation of GI sensorimotor functions and normal GI motility in humans. Disorders such as gastroparesis (including diabetic gastroparesis, idiopathic gastroparesis, and postsurgical gastroparesis), dumping syndrome, intestinal pseudo-obstruction, small intestinal bacterial overgrowth, megacolon (including Hirschsprung disease, toxic megacolon, and colonic pseudo-obstruction), chronic constipation (including defecatory disorders, normal transit constipation, and slow transit constipation), functional dyspepsia, functional diarrhea and irritable bowel syndrome, and fecal incontinence are then discussed in depth. Tables present a comparison of GI motility and functional disorders, the causes of gastroparesis, the etiology of intestinal pseudo-obstruction and fecal incontinence, common medical conditions and medications associated with constipation, and the symptom severity scale in fecal incontinence. Illustrations, graphs, magnetic resonance images, and algorithms are provided. This chapter contains 10 highly rendered figures, 6 tables, 92 references, and 5 MCQs.

Abnormal ghrelin secretion contributes to gastrointestinal symptoms in multiple system atrophy patients

Patients with multiple system atrophy (MSA) often have evidence of compromised gastrointestinal motility. Ghrelin is a gut hormone that influences gastrointestinal motility in humans. The aim of this study was to determine whether ghrelin secretion is affected in MSA patients, and to investigate the relation between ghrelin secretion and gastrointestinal symptoms. Plasma levels of active ghrelin and unacylated ghrelin were measured in patients with MSA (n = 30), other atypical parkinsonian disorders including progressive supranuclear palsy-Richardson syndrome and corticobasal syndrome (n = 24), and control subjects (n = 24) using enzyme-linked immunosorbent assays. Gastrointestinal symptoms were quantified in all subjects using a self-report questionnaire. The ratio of active ghrelin to total ghrelin in the plasma (active ghrelin ratio) was lower in patients with MSA (mean: 8.0 %) than in patients with other atypical parkinsonian disorders (mean: 13.7 %, P = 0.001) and control subjects (mean: 13.9 %, P = 0.001). The active ghrelin ratio was correlated with the severity of gastrointestinal symptoms in MSA (r = −0.5, P = 0.004). Our observations indicate that ghrelin secretion is affected in patients with MSA. The low active ghrelin ratio may contribute to gastrointestinal symptoms in MSA.

The Role of Capsaicin in Spontaneous Pacemaking Activity in Gastrointestinal Tract

Interstitial cells of Cajal (ICCs) are the pacemaking cells in the gastrointestinal (GI) tracts that generate the rhythmic oscillations in the membrane potential which were known as slow waves recorded in native smooth muscle tissue preparations in the past. Auto-rhythmicity in GI tracts is an exclusive property of ICCs and the spread of slow waves through GI tracts occurs electrically, and not by the active regeneration properties of ICCs and smooth muscles. Pacemaking ICCs are organized into electrically coupled networks within discrete areas of the stomach, small intestine, and colon.1,2 ICCs were originally identified by Santiago Ramon y Cajal and were characterized by morphological criteria until the discovery that these cells express the receptor tyrosine kinase Kit.3 Subsequent studies determined that Kit immunoreactivity in the muscularis propria of the GI tract is restricted to 2 cell types: mast cells4 and ICCs. Kit-positive ICCs are distributed throughout the GI tract as well as in other smooth muscle tissues.5 All regions of the GI tract contain ICCs but the location within the muscularis propria varies according to region or species.6 In the myenteric plexus region, ICCs form a network between the muscle layers forming a mesh around the ganglia and are considered as major pacemaker cells. A network of deep muscular plexus ICCs is present in the small intestine between the inner and outer circular muscle layers.6 In the colon and parts of the gastric antrum, submuscular ICCs are located outside the circular muscle layer.7 Intramuscular ICCs are distributed through the longitudinal and circular muscle layers and are considered to be involved in neurotransmission from nerve terminals. Septal ICCs are found between the fascicles of muscle in humans and other large species. These can be considered as one type of intramuscular ICCs.8 Stellate, subserosal ICCs are observed on the boundary between the longitudinal muscle and the serosa in the colon of mice.9 Capsaicin (8-methyl-N-vanillyl-6-ninenamide) activates afferent fiber endings and capsaicin sensitive primary afferent neurons participate in the regulation of GI motility.10 Furthermore, capsaicin induces contraction in the guinea-pig ileum11 and relaxation in human small and large intestines.10 Namely, it is known that capsaicin may have excitatory action on animal GI motility but inhibitory on human. However, information about the effect of capsaicin on human GI motility is somewhat controversial. Some reports showed the oral administration of capsaicin to fail in showing a significant effect on GI motility in human12-14 but there are reports that capsaicin could contribute to protection of the esophagus and could promote retention of the irritant in the stomach and faster transit through the small bowel.15 However, there are no reports on the direct effect of the capsaicin on ICCs that have important roles for regulation of GI motility as pacemaker cells. In this issue of the Journal of Neurogastroenterology and Motility, Choi et al examined the role of capsaicin on ICC in mouse small intestine. They showed that capsaicin inhibited the pacemaker activity of ICC dose-dependently. The effect of capsaicin, however, is not through the transient receptor potential of the vanilloid type 1 (TRPV1) channel because capsazepine did not block the effect of capsaicin. Consistently with this result, they also showed in their previous study that TRPV1-immunopositive cells were not co-localized with c-Kit positive tissue layer.16 The effect of capsaicin was not through nitric oxide release from ICCs, because there was no influence on capsaicin-induced action by L-NAME, an inhibitor of nitric oxide synthase in their study. Choi et al. proposed that further studies are needed to investigate the direct effect of capsaicin on pacemaker ion channels like TRPC4 or TRPM7 responsible for pacemaking activity in ICCs.17 Interestingly, when the action of capsaicin was examined in the intracellular calcium oscillation, capsaicin completely abolished the calcium oscillation in ICCs. Recently, 3 research groups showed simultaneously the calcium activated Cl channels to be required for pacemaking activity using TMEM16A knockout mice.18-20 Capsaicin might inhibit pacemaking activity of ICCs through the decreased activity of calcium activated Cl channels due to completely abolished calcium oscillations by application of capsaicin to ICCs. The effect of capsaicin seems more complicated because capsaicin acts on ICCs as well as afferent nerve endings of GI tract. In the future, more sophisticated studies are needed to clarify the role of capsaicin in GI tract considering ICCs and species differences.

Laser microdissection as a new tool to investigate site-specific gene expression in enteric ganglia of the human intestine

Myenteric ganglia are key-structures for the control of intestinal motility and their mRNA expression profiles might be altered under pathological conditions. A drawback of conventional RT-PCR from full-thickness specimens is that gene expression analysis is based on heterogeneously composed tissues. To overcome this problem, laser microdissection combined with real-time RT-PCR can be used to detect and quantify low levels of gene expression in isolated enteric ganglia. Fresh unfixed full-thickness specimens of sigmoid colon were obtained from patients (n = 8) with diseases unrelated to intestinal motility disorders. 10 microm cryo-sections were mounted on membrane-coated slides and ultra-rapidly stained with toluidine blue. Myenteric ganglia were isolated by laser microdissection and catapulting for mRNA isolation. Real-time RT-PCR was performed for selected growth factors, neurotransmitter receptors and specific cell type markers. Collection of 0.5 mm(2) of ganglionic tissue was sufficient to obtain positive RT-PCR results. Collection of 4 mm(2) resulted in ct-values allowing a reliable quantitative comparison of gene expression levels. mRNA analysis revealed that neurotrophic growth factor, neurotrophin-3, serotonin receptor 3A, PGP 9.5 and S100 beta are specifically expressed in myenteric ganglia of the human colon. Laser microdissection combined with real-time RT-PCR is a novel technique to reliably detect and quantify site-specific expression of low-abundance mRNAs (e.g. growth factors, neurotransmitter receptors) related to the human enteric nervous system. This technical approach expands the spectrum of available tools to characterize enteric neuropathologies underlying human gastrointestinal motility disorders at the molecular biological level.

Development of the enteric nervous system and its role in intestinal motility during fetal and early postnatal stages

Motility patterns in the mature intestine require the coordinated interaction of enteric neurons, gastrointestinal smooth muscle, and interstitial cells of Cajal. In Hirschsprung's disease, the aganglionic segment causes functional obstruction, and thus the enteric nervous system (ENS) is essential for gastrointestinal motility after birth. Here we review the development of the ENS. We then focus on motility patterns in the small intestine and colon of fetal mice and larval zebrafish, where recent studies have shown that the first intestinal motility patterns are not neurally mediated. Finally, we review the development of gastrointestinal motility in humans.

A randomized, placebo‐controlled, crossover, double‐blind trial of the NK1 receptor antagonist aprepitant on gastrointestinal motor function in healthy humans

Little is known about the role of tachykinins on human gastrointestinal motility and no data exist on the possible effect of an NK1 receptor antagonist. To examine the effect of an antiemetic dose of the selective NK1 receptor antagonist aprepitant on gastrointestinal propulsion in healthy humans. Twelve healthy volunteers participated in a crossover, double-blind study. In random order, each volunteer had a 125-mg capsule of aprepitant or placebo on day 1 followed by an 80-mg capsule of aprepitant or placebo on days 2-5. Gamma camera imaging was used to measure gastric emptying, small intestinal transit and colonic transit of a radiolabelled, 1600-kJ mixed liquid and solid meal ingested on day 2. Aprepitant did not change gastric retention at 15 min, gastric half emptying time, gastric mean transit time, time to small intestinal transit of 10%, small intestinal mean transit time or colonic geometric centre after 24, 48 and 72 h. A 125-mg capsule of aprepitant followed by an 80-mg capsule of aprepitant each of the next 2-5 days did not induce major changes in the propulsive function of the gastrointestinal tract in the small number of healthy volunteers investigated.

Structural Determination of Two Active Compounds That Bind to the Muscarinic M3 Receptor in Beer

It is known that beer accelerates gastrointestinal motility in humans. Our previous studies showed that beer congener stimulates gastrointestinal motility by directly stimulating the muscarinic M3 receptor. Further, we isolated 2 active compounds (compounds A and B) from beer by liquid chromatography. The objective of the present study was to identify the 2 active compounds that bind to the muscarinic M3 receptor in beer. Structural analyses of the active compounds were performed by fast atom bombardment mass spectra, 1H-nuclear magnetic resonance (NMR), and 13C-NMR spectroscopy. Active compounds were chemically synthesized from p-coumaric acid and agmatine as starting materials. Binding activity to the muscarinic M3 receptor was used to confirm the activity of the synthetic compounds. It was identified that 2 active compounds had the same structural characteristics: stereoisomers (cis-isomer and trans-isomer), molecular weight=550 and molecular formula=C28H38N8O4. Trans-isomer (compound B) was identified as the known substance hordatine A, a kind of phytoalexin in barley, and cis-isomer (compound A) was found to be a novel compound (tentatively referred to as aperidine). Both naturally present and chemically synthesized aperidine (compound A) and hordatine A (compound B) were demonstrated to have potent binding activities to the muscarinic M3 receptor. The 2 active compounds isolated from beer, namely aperidine (compound A) and hordatine A (compound B), have structurally and functionally been identified as active entities of binding to the muscarinic M3 receptor.

A novel biomagnetic approach to study caecocolonic motility in humans

Motility patterns play a major role in human colonic functions; however, its physiological significance is poorly understood. Several studies have been introducing the Alternating Current Biosusceptometry (ACB) as a valuable tool in gastroenterology and pharmaceutical research. Using gold standard techniques, great effort has been made to validate ACB as a method for measuring gastrointestinal motility in humans and animals. The aim of this study was to evaluate caecocolonic motility and its response to a meal in healthy volunteers. The results showed a dominant frequency of 3.17 +/- 0.13 cycles per minute (mean +/- SD) that remained unchanged even after a standardized meal (P > 0.01). The colonic response to a meal was recorded as a considerable increase in amplitude, reflected by motility index (P < 0.01) and was observed for all the volunteers. The caecocolonic motility could be assessed by the ACB providing new insights into physiological patterns of motility. Moreover, the method is non-invasive, radiation-free, cost-effective and independent of bowel preparation.

Inhibition of human pancreatic and biliary output but not intestinal motility by physiological intraileal lipid loads

Lipid perfusion into the distal ileal lumen at supraphysiological loads inhibits pancreatic exocrine secretion and gastrointestinal motility in humans. In the present study, we sought to determine the effects of physiological postprandial intraileal lipid concentrations on endogenously stimulated pancreaticobiliary secretion, intestinal motility, and release of regulatory mediators. Eight healthy volunteers were intubated with an oroileal multilumen tube for continuous duodenal perfusion of essential amino acids (450 mumol/min), ileal perfusion of graded doses of lipids (0, 50 and 100 mg/min, each dose for 90-120 min), aspiration of duodenal and ileal chyme, and intestinal manometry. Venous blood samples were obtained for measurement of GLP-1 and PYY. Ileal lipid perfusion dose dependently decreased endogenously stimulated trypsin [262 +/- 59 vs. 154 +/- 42 vs. 92 +/- 20 U/min (P < 0.05)] and bile acid output [18.6 +/- 1.9 vs. 8.4 +/- 2.8 vs. 3.0 +/- 1.0 micromol/min (P < 0.05)]. Duodenal motor activity was not inhibited by either lipid dose. Trypsin and bile acid output correlated inversely with the release of GLP-1 and PYY (absolute value of R > 0.84; P < 0.05), whereas the motility index did not. Physiological postprandial ileal lipid concentrations dose dependently inhibited human digestive pancreatic protease and bile acid output, but not intestinal motor activity. Thus physiological postprandial ileal nutrient exposure may be of importance for the termination of digestive secretory responses. Ileocolonic release of GLP-1 and PYY appears to participate in mediating these effects.

Endothelin Receptors in Gastrointestinal Smooth Muscle

Endothelins (ETs) are a family of peptides with 21-amino-acid residues. ET-1 was identified as a potent vasoconstrictor produced by vascular endothelial cells. Three distinct isoforms of ET, i.e. ET-1, ET-2 and ET-3, have been found to exist in a variety of tissues. ET was later found to cause contraction as well as relaxation of smooth muscle in many physiologic systems. In the gastrointestinal tract, ET causes contraction and/or relaxation of the esophagus, stomach, ileum and colon. In the hepatobiliary system, ET causes contraction of the portal vein, hepatic stellate cells, gallbladder and common bile duct. In mammalian species, two classes of ET receptors, ET(A) and ET(B), have been cloned. ET(A) receptors have higher affinities for ET-1 and ET-2 than ET-3, while ET(B) receptors have the same affinities for ET-1, ET-2 and ET-3. In the gastrointestinal system, ET causes smooth muscle contraction through interaction with ET(A) receptors, ET(B) receptors or both ET(A) and ET(B) receptors, depending on the tissues and species. In addition to contraction, ET causes smooth muscle relaxation through interaction with ET(A) receptors or ET(B) receptors. At the present time, there are no studies showing that ET causes smooth muscle relaxation through interaction with both ET(A) and ET(B) subtypes. ET induces contraction in most of the non-sphincter muscle except the fundus of the stomach. On the other hand, ET causes relaxation and contraction in the lower esophageal and internal anal sphincters. ET may play an important role in the control of human gastrointestinal motility and portal vein pressure.

Effects of Pyridoxal-5′-Phosphate and Haloperidol on Synaptic Transmission in Human Colon Smooth Muscle

1 Bogomolets National Medical University, Kyiv, Ukraine. Correspondence should be addressed to M. M. Grusha (e-mail: mishagru@stenos.kiev.ua). Vitamin B 6 (pyridoxal), pyridoxal-5′-phosphate (PyrP), and haloperidol are drugs that can significantly influence the gastrointestinal motility in humans. A modified sucrose-gap technique was used in our experiments conducted on atropinized muscle strips isolated from the circular muscle layer of visually intact regions of the human ascendens, transversum, descendens, or sigmoideum colonic tissue removed in the course of surgical interventions caused by cecum, sigmoid, or rectum cancer. Spontaneous electrical activity was recorded in 85% of the cases. Inhibitory synaptic potentials (ISP) consisted of a single “fast” component and two-component ISP (including “fast” and “slow” components) were observed in 51 and 49% of the cases, respectively. Post-ISP depolarization waves with action potentials on their crests were found in 38% on the examined muscle strips, and depolarization at the boundary between the components of two-component ISP was observed in 32% of the cases. In experiments with drug application on muscle strips, control values of the analyzed parameters were taken as 100%. After 1to 5-min-long application of PyrP (1 · 10 M), the amplitude of ISP decreased to 86 ± 4, in 6-10 min to 73 ± 6% (n = 8), in 11-15 min to 68 ± 6% (n = 7), in 16-20 min to 57 ± 5, and in 21-25 min to 46 ± 7% (n = 4). After 6to 10-min-long application of PyrP, the latency of ISP increased to 128 ± 9% (n = 7), in 11-15 min to 135 ± 2% (n = 5), and in 16-20 min to 144 ± 8% (n = 4). Simultaneously, PyrP significantly increased the ISP duration (n = 8) and suppressed post-ISP depolarization waves with action potentials on their crests and depolarizations at the boundary between two components of complex ISP. Pyridoxal (1 · 10 M) less effectively than PyrP decreased the ISP amplitude. After 11to 15-min-long application of haloperidol (1 · 10 M), the amplitude of ISP decreased to 67 ± 8, in 16-20 min to 50 ± 7% (n = 7), in 21-25 min to 34 ± 7, in 26-30 min to 25 ± 7% (n = 6), in 36-40 min to 3 ± 2% (n = 5), and after 46to 50-min-long applications the amplitude dropped to zero (n = 5). After 16to 20-min-long application of haloperidol, the time of half-decay of ISP decreased to 74 ± 3 % (n = 6), spontaneous electrical activity and post-ISP depolarization waves with action potentials disappeared (n = 7), as well as depolarizations interposed between the components of two-component ISP did. The latency of ISP increased to 129 ± 2% (n = 5) in 26-30 min. The tested drugs can be considered effective modulators of synaptic transmission in the colonic smooth muscles.

Beer Congener Stimulates Gastrointestinal Motility Via the Muscarinic Acetylcholine Receptors

Ethanol and alcoholic beverages are known to affect upper gastrointestinal motility in humans. Beer has been reported to accelerate gastric emptying compared with other beverages that contain the same ethanol concentrations. In this study, we investigated the mechanism that underlies the effects of beer congener on gastrointestinal motility. Gastric emptying activity was measured by means of movement of a semisolid test meal (0.05% phenol red/1.5% methylcellulose) in mice. To elucidate the mechanism for the effect of beer congener on gastrointestinal motility, we conducted receptor binding assays and contraction study by using longitudinal muscle from guinea pig ileum. Beer congener (1 g/kg orally) enhanced gastric emptying of a semisolid meal in mice. The receptor binding assay revealed that beer congener bound to dopamine D2 receptor and 5-hydroxytryptamine (5-HT)3 receptor. These IC50 values were more than 5 mg/ml. However, beer congener bound to 5-HT2 receptor, 5-HT4 receptor, and muscarinic M3 receptor with IC50 values of 2, 0.9, and 2 mg/ml, respectively. Beer congener (0.05-2 mg/ml) induced the contraction of longitudinal muscle from guinea pig ileum in a dose-dependent manner. This effect was not affected by either tetrodotoxin (10(-6)M) or ketanserin (10(-7)-10(-5)M), an antagonist for the 5-HT2 receptor. On the other hand, 4-DAMP (10(-8)-10(-5)M), an antagonist for the muscarinic M3 receptor, inhibited the contraction of the longitudinal muscle induced by beer congener (2 mg/ml) dose dependently. Beer congener stimulates gastrointestinal motility via the muscarinic M3 receptor.

Glucagon-like peptide 1 increases the period of postprandial satiety and slows gastric emptying in obese men

The gut peptide glucagon-like peptide 1(7-36) amide (GLP-1) is released into the circulation after food intake. GLP-1 has been shown to have an incretin effect and inhibits gastrointestinal motility in humans. In rats, intracerebral administration of GLP-1 results in reduced food intake. Obese humans have been found to have an attenuated plasma GLP-1 response to a mixed meal. To approximate the physiologic state, GLP-1 or saline was administered intravenously and randomly at the beginning of a test meal served on a universal eating monitor to 6 obese subjects to test our hypothesis that GLP-1 influences termination of food intake (and thus food intake during a meal) and feelings of satiety in humans. As a marker for gastric emptying, 1.5 g acetaminophen was given at the start of the meal. Blood samples for analysis of acetaminophen, insulin, glucose, glucagon, and C-peptide were obtained. Hunger, fullness, and food choice were assessed with visual analogue scales and food-choice questionnaires. GLP-1 infusion resulted in a prolonged period of reduced feelings of hunger, desire to eat, and prospective consumption after the meal. The rate of gastric emptying was slower during infusion of GLP-1. Postprandial blood glucose concentrations were reduced during the GLP-1 infusion, but the amount of energy consumed, eating rate, and plasma concentrations of insulin, glucagon, and C-peptide were unchanged. GLP-1 given exogenously at the start of a meal did not seem to affect meal termination or the amount of food eaten. However, postprandial feelings of hunger decreased, suggesting that exogenous GLP-1 may influence feelings of hunger and satiety in humans. Am J Clin Nutr 1998;68:525–30.

Gastrointestinal motor activity in conscious ferrets

Gastrointestinal motility was measured with force transducers in conscious ferrets. The gastrointestinal motility pattern in both the interdigestive and digestive states was similar to that reported for humans. The activity front, phase III contractions of the migrating motor complex, occurred cyclically in the antrum and migrated to the duodenum and ileum in the interdigestive state, and relatively low-amplitude contractions were sustained in the antrum, duodenum and ileum in the digestive state. Colonic motility was characterized by basal relatively low-amplitude contractions and a single high-amplitude contraction preceding defecation. Cisparide (0.3–3 mg/kg s.c.) enhanced antral and colonic motility. This ferret model will help the investigation and evaluation of drug effects on gastrointestinal motility in humans.

Neural mediation of the motilin motor effect on the human antrum.

To elucidate the mode of action of motilin on the stimulation of human gastrointestinal motility, we studied the effect of exogenous motilin during muscarinic or serotoninergic pharmacological blockade. Manometric recording of the interdigestive antroduodenal motility was carried out in 27 healthy volunteers until the appearance of a spontaneous antral phase III. The tested blocker was then administered intravenously and was followed 30 min later by a 10-min infusion of synthetic human motilin (50 ng/kg). Motilin administered on a background of saline induced a premature phase III migrating from the antrum to the duodenum in every tested subject (n = 5). A low dose of atropine (5 micrograms.kg-1.h-1 for 90 min) inhibited the motilin effect in two of five subjects [not significant (NS)], whereas a high dose of atropine (15 micrograms/kg given in 30 min) blocked the motilin-induced premature antral phase III in all instances (n = 5, P < 0.01). Exogenous motilin given with low-dose ondanseton (8 mg given in 15 min followed by 1 mg/h for 90 min) or high-dose ondansetron (32 mg given in 30 min) was without effect in three of seven (NS) or in two of five (NS) subjects, respectively. During the administration of 15 micrograms/kg atropine, when exogenous motilin always failed to induce a premature antral phase III motor, a phase III-type activity was generated at the duodenum in four of five subjects. We conclude that the induction by motilin of phase III activity in human antrum is dependent on muscarinic mediation and that the contractile effect of motilin on human duodenum involves a noncholinergic mechanism, different therefore from the antral pathway.