• Journal of Neurogastroenterology and Motility
• /
• v.24 no.4
• /
• pp.643-655
• /
• 2018

Background/Aims Irritable bowel syndrome (IBS) is a common disease characterized by intestinal dysmotility, the mechanism of which remains elusive. We aim to determine whether the high-affinity choline transporter 1 (CHT1), a determinant of cholinergic signaling capacity, modulates intestinal motility associated with stress-induced IBS. Methods A rat IBS model was established using chronic water avoidance stress (WAS). Colonic pathological alterations were evaluated histologically and intestinal motility was assessed by intestinal transit time and fecal water content (FWC). Visceral sensitivity was determined by visceromotor response to colorectal distension. RT-PCR, western blotting, and immunostaining were performed to identify colonic CHT1 expression. Contractility of colonic muscle strips was measured using isometric transducers. enzyme-linked immunosorbent assay was used to measure acetylcholine (ACh). We examined the effects of MKC-231, a choline uptake enhancer, on colonic motility. Results After 10 days of WAS, intestinal transit time was decreased and fecal water content increased. Visceromotor response magnitude in WAS rats in response to colorectal distension was significantly enhanced. Protein and mRNA CHT1 levels in the colon were markedly elevated after WAS. The density of CHT1-positive intramuscular interstitial cells of Cajal and myenteric plexus neurons in WAS rats was higher than in controls. Ammonium pyrrolidine dithiocarbamate partly reversed CHT1 upregulation and alleviated colonic hypermotility in WAS rats. Pharmacological enhancement of CHT1 activity by MKC-231 enhanced colonic motility in control rats via upregulation of CHT1 and elevation of ACh production. Conclusion Upregulation of CHT1 in intramuscular interstitial cells of Cajal and myenteric plexus neurons is implicated in chronic stress-induced colonic hypermotility by modulation of ACh synthesis via nuclear factor-kappa B signaling.

• Journal of Veterinary Clinics
• /
• v.20 no.1
• /
• pp.22-25
• /
• 2003

The aims of this study were to investigate the efficacy of acupuncture on myoelectrical activity of inflamed or normal colon in the rat, and whether the effect of acupuncture on colonic motility was related to endogenous opioids. Twenty-two male Sprague-Dawley rats were divided into three groups. Experimental groups were normal group (n = 8), colitis group (n = 6) and naloxone group (n = 8). Stainless steel bipolar electrodes were implanted on the serosal layer of the proximal colon of rats. Colitis was induced 7 days after electrode implantation using trinitrobenzene sulphonic acid (TNBS) and ethanol. Electromyograms (EMG) were recorded by using polygraph 11 days after implantation of electrodes. In normal group, normal colonic motility was recorded for 60 min, and then traditional acupuncture at GV-1 was applied for 20 min and EMG was recorded for further 60 min in untreated rats. In colitis group, after recording of basal colonic motility for 60 min, 20 min of acupuncture treatment and further EMG recording was performed for 60 min in TNBS/ethanol treated rats. In naloxone group, following subcutaneous administration of naloxone (3 mg/kg), recording of EMG and acupuncture treatment were performed in TNBS/ethanol treated rats. In the normal group, acupuncture at GV-1 did not induce significant changes in colonic motility. TNBS/ethanol treatment had no significant effect on the frequency of colonic motility. And in colitis group, GV-1 acupuncture significantly decreased colonic motility (p < 0.01). In naloxone group, after injection of naloxone, acupuncture at GV-1 did not change colonic motility in TNBS/ethanol treated rats. On the inflamed colon, naloxone blocked the effect of acupuncture. The present results suggested that endogenous opioids released by acupuncture at GV-1 decrease the motility of inflamed colon in rats, but not normal colon.

• Biomolecules & Therapeutics
• /
• v.28 no.4
• /
• pp.328-336
• /
• 2020

Diabetes mellitus affects the colonic motility developing gastrointestinal symptoms, such as constipation. The aim of the study was to examine the role of intracellular signaling pathways contributing to colonic dysmotility in diabetes mellitus. To generate diabetes mellitus, the rats were injected by a single high dose of streptozotocin (65 mg/kg) intraperitoneally. The proximal colons from both normal and diabetic rats were contracted by applying an electrical field stimulation with pulse voltage of 40 V in amplitude and pulse duration of 1 ms at frequencies of 1, 2, 4, and 6 Hz. The muscle strips from both normal rats and rats with diabetes mellitus were pretreated with different antagonists and inhibitors. Rats with diabetes mellitus had lower motility than the control group. There were significant differences in the percentage of inhibition of contraction between normal rats and rats with diabetes mellitus after the incubation of tetrodotoxin (neuronal blocker), atropine (muscarinic receptor antagonist), prazosin (α₁ adrenergic receptor antagonist), DPCPX (adenosine A1 receptor antagonist), verapamil (L-type Ca²⁺ channel blocker), U73122 (PLC inhibitor), ML-9 (MLCK inhibitor), udenafil (PDE₅ inhibitor), and methylene blue (guanylate cyclase inhibitor). The protein expression of p-MLC and PDE₅ were decreased in the diabetic group compared to the normal group. These results showed that the reduced colonic contractility resulted from the impaired neuronal conduction and decreased muscarinic receptor sensitivity, which resulted in decreased phosphorylation of MLC via MLCK, and cGMP activity through PDE₅.

• The Korean Journal of Physiology and Pharmacology
• /
• v.16 no.6
• /
• pp.437-446
• /
• 2012

Ulcerative colitis is an inflammatory bowel disease (IBD) characterized by recurrent episodes of colonic inflammation and tissue degeneration in human or animal models. The contractile force generated by the smooth muscle is significantly attenuated, resulting in altered motility leading to diarrhea or constipation in IBD. The aim of this study is to clarify the altered contractility of circular and longitudinal smooth muscle layers in proximal colon of trinitrobenzen sulfonic acid (TNBS)-induced colitis mouse. Colitis was induced by direct injection of TNBS (120 mg/kg, 50% ethanol) in proximal colon of ICR mouse using a 30 G needle anesthetized with ketamin (50 mg/kg), whereas animals in the control group were injected of 50% ethanol alone. In TNBS-induced colitis, the wall of the proximal colon is diffusely thickened with loss of haustration, and showed mucosal and mucular edema with inflammatory infiltration. The colonic inflammation is significantly induced the reduction of colonic contractile activity including spontaneous contractile activity, depolarization-induced contractility, and muscarinic acetylcholine receptor-mediated contractile response in circular muscle layer compared to the longitudinal muscle layer. The inward rectification of currents, especially, important to $Ca^{2+}$ and $Na^+$ influx-induced depolarization and contraction, was markedly reduced in the TNBS-induced colitis compared to the control. The muscarinic acetylcholine-mediated contractile responses were significantly attenuated in the circular and longitudinal smooth muscle strips induced by the reduction of membrane expression of canonical transient receptor potential (TRPC) channel isoforms from the proximal colon of the TNBS-induced colitis mouse than the control.

• Herbal Formula Science
• /
• v.32 no.1
• /
• pp.29-37
• /
• 2024

Objectives : The purpose of this study was to examine the effects of insurance herbal medicines on colonic interstitial Cells of Cajal (ICC) in mice. Methods : Among the insurance herbal medicines, we chose Gamisoyo-san (GSS), Banhasasim-tang (BHSST) and Bojungikki-tang (BGIKT). We made the ICC culture in large intestine in mice and used the electrophysiological method to record pacemaker potentials. Also we used MTT assay to check cell viability and examined the ICC protein expression by western blot. Results : 1. GSS (1-10 mg/ml) induced the pacemaker potential depolarization and decreased frequency with concentration-dependent manners in colonic ICC. EC50 is 2.99 mg/ml. BHSST (1-10 mg/ml) induced the pacemaker potential depolarization and decreased frequency with concentration-dependent manners in colonic ICC. EC50 is 2.76 mg/ml. BGIKT (1-10 mg/ml) induced the pacemaker potential depolarization and decreased frequency with concentration-dependent manners in colonic ICC. EC50 is 4.49 mg/ml. 2. GSS, BHSST and BGIKT had no effects on cell viability in colonic ICC. 3. GSS and BGIKT increased the Anoctamin-1 (ANO1) protein expression and BHSST increased the transient receptor potential melastatin-subfamily member 7 (TRPM7) protein expression in colonic ICC. Conclusions : These results suggest that GSS, BHSST, and BGIKT have shown the potential to regulate gastrointestinal (GI) motility by regulating colonic ICC and may show the potential to treat colon-derived GI diseases such as irritable bowel syndrome (IBS).

• The Korean Journal of Physiology and Pharmacology
• /
• v.18 no.5
• /
• pp.383-390
• /
• 2014

Gastrointestinal motility consists of phasic slow-wave contractions and the migrating motor complex (MMC). Eupatilin (Stillen$^{(R)}$) 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$^{(R)}$) 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.

• Advances in pediatric surgery
• /
• v.8 no.1
• /
• pp.54-61
• /
• 2002

Hirschsprung's disease (HD) is usually diagnosed in the newborn period and early infancy. The common presentation of HD in newborns consists of a history of delayed passage of meconium within the first 48 hours of life. The differential diagnosis in newborns is one of the clinical challenges of this disorder. A number of medical conditions which cause functional obstruction of the intestines are easily excluded. Neonates with meconium ileus, meconium plug syndrome, distal ileal atresia and low imperforate anus often present in a manner similar to those with HD in the first few days of life. Abdominal radiographs may help to diagnose complete obstruction such as intestinal atresia. Microcolon on contrast enema can be shown in cases with total colonic aganglionosis, ileal atresia or meconium ileus. Suction rectal biopsy or frozen section biopsy at operation is essential for differential diagnosis in such cases. HD is also considered in any child who has a history of constipation regardless of age. Older children with functional constipation may have symptoms that resemble those of HD and contrast enema is usually diagnostic. However, children with other motility disorders generally referred to as chronic idiopathic intestinal pseudoobstruction present with very similar symptoms and radiographic findings. These disorders are classified according to their histologic characteristics.; visceral myopathy, visceral neuropathy, intestinal neuronal dysplasia (IND), hypoganglionosis, immature ganglia, internal sphincter achalasia. Therefore, the workup for motility disorders should include rectal biopsy not only to confirm the presence of ganglion cells but also evaluate the other pathologic conditions.

• Journal of Acupuncture Research
• /
• v.15 no.2
• /
• pp.311-318
• /
• 1998

Amis:ST25(Chonchu) and ST37(Sanggoho) are usually used acupoints to management several disease which induced to abnormal intestinal motility as diarrhea, constipation. Colonic transit time by radio opaque marker is able to study easily and useful method for evaluation of colonic motility. The aim of this study was to assess the effect on colonic transit time by manual acupuncture or electroacupuncture stimulation of ST25, ST37 in normal adult. Method: Colonic transit time, including Rt colon, Lt colon, rectosigmoid colon was measured by radio opaque marker in 11 normal adults. Colon transit time was measured before stimulation and after stimulation on ST25, ST37 by manual acupuncture and electroacupuncture. Each person was treated manual acupuncture or electroacupuncture stimulation for 3 days before colonic transit time measurement with 1 week interval. Result: Colon transit time before stimulation was measured $10.60{\pm}12.11$, $3.92{\pm}7.72$, $3.27{\pm}6.37$, $3.41{\pm}5.57$ hours total colon, Rt colon, Lt colon, rectosigmoid colon, respectively. Colon transit time after manual acupuncture is measured $10.48{\pm}12.35$, $3.72{\pm}7.52$, $3.37{\pm}6.76$, $3.39{\pm}5.84$ hours total colon, Rt colon, Lt colon, rectosigmoid colon, respectively. Colon transit time after electroacupuncture stimulation is measured $10.30{\pm}13.21$, $3.92{\pm}8.02$, $3.07{\pm} $, $3.31{\pm}5.49$ hours total colon, Rt colon, Lt colon, rectosigmoid colon, respectively. Significant change was observed Lt colon transit time after electroacupuncture as compared before acupuncture(P<0.05). Conclusion: Theses results suggest that manual acupuncture and electroacupuncture of ST25, ST37 in normal adults does not change colonic transit time.

• Journal of Korean Medicine Rehabilitation
• /
• v.18 no.4
• /
• pp.13-24
• /
• 2008

Objectives : The purpose of this study was to investigate the effect of Poncirus Trifoliata(PT) on improvement of fecal impaction in spinal cord injured(SCI) rats. Methods : Fifteen adult Sprague-Dawley female rats were used weighing 200~250 g. A complete spinal cord transection was performed surgically at the T10 cord level. Experimental groups were assigned into 3 groups: Control(n=5), SCI+vehicle(n=5) and SCI+PT(n=5). PT was administered 100mg/kg in 0.5ml every 24 hours from 1st operation day to 7th day. We measured the body weight and food intake as well as the number and the weight of fecal pellet every morning. After 1 week of operation, whole colon was divided into proximal and distal segments under anesthesia. Each segment of colon was mounted with longitudinal direction in a organ bath. We measured spontaneous contraction and compared the area under the curve in each segments. Enhanced responses were observed by acetylcholine($10^{-6}M$), 40 mM KCl solution, L-NAME($10^{-4}M$). Results : The fecal number and weights were significantly higher in the group of SCI+PT than SCI+vehicle group(p<0.05). In organ bath study, area under the curves of the spontaneous contraction in SCI+vehicle and SCI+PT groups were significantly increased compared to control group. Contractility of distal colon in response to acetylcholine or KCl in SCI+vehicle group was significantly decreased compared to other groups(p<0.05). Conclusions : These results suggest that PT might be useful to promote bowel emptying in spinal cord injured rats.

• Korean Journal of Plant Resources
• /
• v.24 no.1
• /
• pp.61-68
• /
• 2011

Loperamide-induced constipation reduced gastric emptying, small-intestinal and colonic motility, and these effects were prevented by Actindia chinensis(Gold Kiwi Fruit, GKF). In this study, the effects of Actindia chinensis on constipated male Sprague-Dawley rats induced by loperamide(2 mg/kg, s.c.,5 days) were investigated. Rats were randomly assigned to the normal control rats(regular diet), constipated rats(regular diet plus loperamide), constipated rats treated with 2.5% GKF(regular diet supplemented with 2.5% GKF plus loperamide), constipated rats treated with 5% GKF (regular diet supplemented with 5% GKF plus loperamide). There was less fecal excretion and lower fecal water content in loperamide-treated rats than in control rats. Oral administration of GKF blocked the decrease of fecal excretion and fecal water content in the loperamide-treated rats. Mucus production of crypt cell and mucus contents at fecal and mucosa surface were reduced by loperamide-treated rat. But colonic crypt cell contained increased mucin in the GKF treated group and mucus layer stained with alcian blue was significantly thicker in GKF treated rats compared with in loperamide-treated rats. In isolated rat ileum, loperamide produced inhibition of ileal motility. Pretreatment with methanolic extracts of GKF in isolated rat ileum prevented inhibition by loperamide. These findings indicated that the GKF was effective for alleviation of inhibition of colonic peristalsis by loperamide and that GKF might be of value in the prevention of constipation.