• Journal of Neurogastroenterology and Motility
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• 제24권4호
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• pp.643-655
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• 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.

• 한국임상수의학회지
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• 제20권1호
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• pp.22-25
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• 2003

본 연구는 정상 및 결장염을 유발한 rat에서 침술이 결장운동성에 미치는 영향을 알아보고, 이에 내인성 opioid가 관여하는지의 여부를 알아보기 위하여 수행하였다. 22마리의 Sprague-Dawley rat을 정상군 (n=8), 결장염군 (n=6) 및 maloxone군(n=8)의 세군으로 나누어 실험을 실시하였다. Rat의 근위 결장의 장막하에 스테인레스 전극을 장착하고, 전극장착 7일 후에 trinitrobenzene sulphonic acid(TNBS)과 ethanol을 이용하여 결장염을 유발하였다. 결장의 근전도는 전극장착 11일 후에 trinitrobenzene sulphonic acid(TNBS)과 ethanol을 이용하여 결장염을 유발하였다. 결장의 근전도는 전극장착 11일 후에 polygraph를 이용하여 측정하였다. 정상군에서는 정상 결장의 기초 근전도를 60분간 기록한 후에 GV-1에 20분간 전통 침술을 실시하고, 다시 60분간 근전도를 가록하였으며, 결장염군에서는 TNBS/ethanol이 미리 투여된 rat에 정상군에서와 같은 방법으로 근전도 기록 및 침술을 실시하였다. Naloxone 군에서는 결장염군과 같은 방법으로 TNBS/ethanol이 미리 투여된 rat에 침술을 실시하기전 naloxone(3 mg/kg, SC)을 투여하고 다른 군에서와 마찬가지로 근전도와 침술을 실시하였다. 정상군에서는 침술이 결장의 운동성에 영향을 미치지 않았다. 그러나 TNBS/ethanol을 투여하여 결장염이 유발된 결장염군에서는 침술에 의해서 결장의 운동성이 유의적으로 저하되었다(p＜0.01). Naloxone군에서는 침술에 의한 결장운동성의 저하는 관찰할 수 없었다. 이상의 결과로 보아 rat에서 GV-1 혈위의 침술에 의해 유발된 내인성 opioid는 염증상태의 결장 운동성을 감소시킨 것으로 사료된다.

• Biomolecules & Therapeutics
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• 제28권4호
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• pp.328-336
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• 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
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• 제16권6호
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• pp.437-446
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• 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.

• 대한한의학방제학회지
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• 제32권1호
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• pp.29-37
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• 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
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• 제18권5호
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• pp.383-390
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• 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
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• 제8권1호
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• pp.54-61
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• 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
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• 제15권2호
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• pp.311-318
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• 1998

목적: 현재 소화기 증상이 없고 정상적인 배변 양상과 습관을 갖고 있으며 과거력상 만성적인 소화기 계통의 질환이 없었던 정상 성인에게 대장운동과 관계있다고 알려진 천추와 상거허에 침자극하고 대장 통과시간의 변화를 관찰하고자 하였다. 방법: 정상 성인 11명의 침자극전 대장 통과시간을 방사선 비투과성 표지자인 Sitzmarks capsule을 사용하여 우측 및 좌측 대장과 직결장, 전대장 통과시간 등으로 나누어 측정한후 대장의 하합혈인 상거허와 복모혈인 천추에 단순유침 15분 및 전침으로 침자극하고 같은 방법으로 대장 통과시간을 측정하여 비교하였다. 결과: 침자극전의 대장 통과시간 측정은 전대장 통과시간이 $10.60{\pm}12.11$시간 이었으며 우측 및 좌측 대장과 직결장의 통과시간이 각각 $3.92{\pm}7.72,\;3.27{\pm}6.37,\;3.41{\pm}5.57$시간 이었다. 단순 15분 유침후 대장 통과시간의 측정은 전대장 통과시간이 $10.48{\pm}12.35$시간, 우측 및 좌측 대장과 직결장의 대장통과 시간이 각각 $3.72{\pm}7.52,\;3.37{\pm}6.76,\;3.39{\pm}5.84$ 시간으로 유의하지 않았다(P>0.05) 전침 자극후 대장 통과시간의 측정은 전대장 통과시간이 $10.30{\pm}13.21$, 우측 및 좌측 대장과 직결장의 통과 시간이 각각 $3.92{\pm}8.02,\;3.07{\pm}5.41,\;3.31{\pm}5.49$ 시간으로 좌측 대장 통과시간이 유의한(P<0.05) 단축 소견을 보였고 우측, 직결장의 통과시간은 유의하지 않았다(P>0.05). 결론: 본 연구의 결과로서 좌측 대장의 통과시간이 천추와 상거허에 전침 자극시 유의하게 단축되는 것을 확인 할 수 있었다. 이것은 전침이 신경계나 체액성 작용에 의해서 신경의 흥분성을 증가시켜 좌측 대장에서 직결장쪽으로 대장 내용물의 이동을 촉진하는 것으로 생각 할 수 있다. 그러나 단순 유침에서는 침자극전 대장 통과시간과 차이를 보이지 않음으로서 모든 침자극이 정상인의 대장운동이 변화를 일으키지는 않는 것으로 생각되었으며 더욱이 전침자극후 좌측 대장외에 우측 대장, 직결장은 단순 유침과 전침자극에 모두 변화가 없었고 전대장 통과 시간의 변화도 유의성이 없어 천추와 상거허의 침자극은 정상인의 대장운동에 영향을 주지는 않을 것으로 사려되었다.

• 한방재활의학과학회지
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• 제18권4호
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• pp.13-24
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• 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.

• 한국자원식물학회지
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• 제24권1호
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• pp.61-68
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• 2011

참다래 동결건조물을 2.5%, 5% 농도로 사료와 혼합하여 실험동물에 투여하고 실험 5일간 loperamide(2 mg/kg/day, s.c.)로 변비를 유도하여 참다래의 변비치료 및 예방 효과를 측정하였다. Lopermide를 단독 투여한 군은 정상대조군과 비교하여 변의 개수 및 중량이 유의적으로 감소하였으며 원위 결장 내 변 잔류의 증가 및 cecocolonic segment의 무게가 증가하였다. 참다래 동결건조물 및 loperamide를 투여한 군은 loperamide를 단독 투여한 군과 비교하여 변의 개수 및 중량이 유의적으로 증가하였으며 원위 결장 내 잔류 변 및 cecocolonic segment의 무게도 감소하였다. 이러한 결과는 참다래가 in vivo에서 변비 개선 효과가 있음을 보여준다. 변의 수분 함량에서도 loperamide로 변비를 유발시킨 군에서 감소하는 경향을 보였고 참다래 동결건조물 투여군에서 농도 의존적으로 증가하는 것을 확인 할 수 있었다. 조직학적 검사에서도 참다래 동결건조물 투여군의 원위 대장관에서 crypt cell내 점액의 증가와 장관내 분변의 점액질의 증가도 관찰되었다. In vitro 실험결과, 회장 적출 절편에서 참다래 동결건조물(2.5 mg/ml)을 전 처리 시 loperamide에 의한 장력과 진폭 억제가 부분적으로 차단되었으며 이러한 결과는 참다래 동결건조물의 변비 개선효과가 장의 운동성 촉진과 대장관 내 점액분비 증가에 의한 대장관 내용물의 이동성증가와 관련이 있음을 시사한다.