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      The effects of eupatilin (stillen®) on motility of human lower gastrointestinal tracts.

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          Abstract

          Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen®) has been widely used to treat gastritis and peptic ulcers, and various cytokines and neuropeptides are thought to be involved, which can affect gastrointestinal motility. We performed a study to identify the effects of eupatilin on lower gastrointestinal motility with electromechanical recordings of smooth muscles in the human ileum and colon. Ileum and colon samples were obtained from patients undergoing bowel resection. The tissues were immediately stored in oxygenated Krebs-Ringer's bicarbonate solution, and conventional microelectrode recordings from muscle cells and tension recordings from muscle strips and ileal or colonic segments were performed. Eupatilin was perfused into the tissue chamber, and changes in membrane potentials and contractions were measured. Hyperpolarization of resting membrane potential (RMP) was observed after administration of eupatilin. The amplitude, AUC, and frequency of tension recordings from circular and longitudinal smooth muscle strips and bowel segments of the ileum and colon were significantly decreased after admission of eupatilin. Eupatilin elicited dose-dependent decreases during segmental tension recordings. In conclusion, eupatilin (Stillen®) showed inhibitory effects on the human ileum and colon. We propose that this drug may be useful for treating diseases that increase bowel motility, but further studies are necessary.

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          Most cited references30

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          A case for interstitial cells of Cajal as pacemakers and mediators of neurotransmission in the gastrointestinal tract.

          Electrical rhythmicity in gastrointestinal muscles has been studied for a century, but the pacemakers driving this phenomenon have been elusive. Anatomic studies suggest that interstitial cells of Cajal (ICC) may be pacemakers and conductors of electrical activity. ICC may also mediate neurotransmission from enteric neurons. Functional evaluations of ICC include the following. (1) Electrophysiology experiments on dissected muscle strips show that slow waves originate from specific sites. These pacemaker areas are populated by networks of ICC that make gap junctions with smooth muscle cells. Removal of pacemaker regions interferes with slow wave generation and propagation. (2) Chemicals that label ICC histochemically can damage ICC and abolish rhythmicity. (3) isolated ICC are spontaneously active, and several voltage-dependent ion channels, including a low-threshold Ca2+ conductance, are expressed. (4) ICC are innervated by enteric neurons, and they respond to neurotransmitters. ICC may produce nitric oxide and amplify inhibitory neurotransmission. (5) Some classes of ICC fall to develop in animals with mutations in c-kit or stem cell factor, the ligand for c-Kit receptors. Without ICC, electrical slow waves are absent. Many questions remain about the function of ICC, but modern technologies should now facilitate rapid progress toward determining the role of these cells in normal physiology and pathological conditions.
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            An evidence-based position statement on the management of irritable bowel syndrome.

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              Altered 5-hydroxytryptamine signaling in patients with constipation- and diarrhea-predominant irritable bowel syndrome.

              Evidence suggests that postprandial platelet-depleted plasma 5-hydroxytryptamine (5-HT) concentrations may be abnormal in irritable bowel syndrome (IBS). However, interpretation of the data has been hampered by the variable methodology and rather small numbers used in previous studies. Therefore, the aim of this study was to measure concentrations of platelet-depleted plasma 5-HT and its metabolite 5-HIAA under fasting and fed conditions in a large group of patients with diarrhea-predominant (d-) and constipation-predominant (c-) IBS, compared with controls. The ratio of plasma 5-HIAA:5-HT and platelet stores was also assessed. Twenty-nine c-IBS patients (aged, 19-53 years), 55 d-IBS patients (aged, 19-52 years), and 35 healthy volunteers (aged, 18-46 years) had platelet-depleted plasma 5-HT/5-HIAA concentrations measured using reverse-phase, high-performance liquid chromatography with fluorimetric detection before and after a standard meal. d-IBS patients had raised platelet-depleted plasma 5-HT concentrations under fasting and fed conditions (P < .05). However, the postprandial relative to fasting concentration was similar to controls. In contrast, c-IBS patients failed to show an increase in platelet-depleted plasma 5-HT concentration with meal ingestion compared with controls (P < .01). c-IBS was associated with decreased 5-HIAA (P < .01) but normal 5-HIAA:5-HT ratio and d-IBS with normal 5-HIAA concentrations but reduced 5-HIAA:5-HT ratio (P < .005). C-IBS but not d-IBS patients had increased platelet 5-HT. These results support the concept that d-IBS is characterized by reduced 5-HT reuptake, whereas impaired release may be a feature of c-IBS. These results also provide a rational basis for current pharmacologic approaches involving modulation of different 5-HT receptors in c- and d-IBS.
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                Author and article information

                Journal
                Korean J. Physiol. Pharmacol.
                The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology
                The Korean Physiological Society and The Korean Society of Pharmacology
                1226-4512
                1226-4512
                Oct 2014
                : 18
                : 5
                Affiliations
                [1 ] Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea.
                [2 ] Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Department of Physiology, Seoul National University College of Medicine, Seoul 110-744, Korea.
                [3 ] Division of Colorectal Surgery, Department of Surgery, Seoul National University College of Medicine, Seoul 110-744, Korea. ; Healthcare Research Institute, Seoul National University Hospital Healthcare System Gangnam Center, Seoul 135-984, Korea.
                [4 ] Dong-A, Pharmaceutical Co, Seoul 130-823, Korea.
                Article
                10.4196/kjpp.2014.18.5.383
                4211121
                25352757
                e318e283-0027-4aff-af2f-39ab187eda21
                History

                Colon,Eupatilin,Ileum,Motility,Smooth muscle
                Colon, Eupatilin, Ileum, Motility, Smooth muscle

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