1.Effect of Itopride Hydrochloride on the Ileal and Colonic Motility in Guinea Pig In Vitro.
Hyun Chul LIM ; Young Gyun KIM ; Jung Hyun LIM ; Hee Sun KIM ; Hyojin PARK
Yonsei Medical Journal 2008;49(3):472-478
PURPOSE: Itopride hydrochloride (itopride) inhibits acetylcholinesterase (AChE) and antagonizes dopamine D(2) receptor, and has been used as a gastroprokinetic agent. However, its prokinetic effect on the small bowel or colon has not yet been thoroughly investigated. The aim of this study was to investigate the effects of itopride on motor functions of the ileum and colon in guinea pigs. MATERIALS AND METHODS: The distal ileum was excised and the activity of peristaltic contraction was determined by measuring the amplitude and propagation velocity of peristaltic contraction. The distal colon was removed and connected to the chamber containing Krebs-Henseleit solution (K-H solution). Artificial fecal matter was inserted into the oral side of the lumen, and moved toward the anal side by intraluminal perfusion via peristaltic pump. Colonic transit times were measured by the time required for the artificial feces to move a total length of 10cm with 2-cm intervals. RESULTS: In the ileum, itopride accelerated peristaltic velocity at higher dosage (10(-10)-10(-6)M) whereas neostigmine accelerated it only with a lower dosage (10(-10)-10(-9)M). Dopamine (10(-8)M) decelerated the velocity that was recovered by itopride infusion. Itopride and neostigmine significantly shortened colonic transit at a higher dosage (10(-10)-10(-6)M). Dopamine (10(-8)M) delayed colonic transit time that was also recovered after infusion of itopride. CONCLUSION: Itopride has prokinetic effects on both the ileum and colon, which are regulated through inhibitory effects on AChE and antagonistic effects on dopamine D(2) receptor.
Animals
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Benzamides/*pharmacology
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Benzyl Compounds/*pharmacology
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Cholinesterase Inhibitors/pharmacology
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Colon/*drug effects/physiology
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Dopamine/pharmacology
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Dose-Response Relationship, Drug
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Gastrointestinal Motility/*drug effects
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Guinea Pigs
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Ileum/*drug effects/physiology
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Neostigmine/pharmacology
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Receptors, Dopamine D1/antagonists & inhibitors/physiology
2.Effects of Tamoxifen on the Voltage-dependent Ionic Currents in Mouse Colonic Smooth Muscle Cells.
Dong Min LEE ; Sung Jong CHANG ; Chan Guk PARK ; Man Woo KIM ; Gun Han LIM ; Seok CHOI ; Cheol Ho YEUM ; Pyung Jin YOON ; Jae Yeoul JUN
The Korean Journal of Gastroenterology 2005;46(5):388-395
BACKGROUND/AIMS: Tamoxifen is a widely used anticancer drug for breast cancer with frequent gastrointestinal side effects. Changes in gastrointestinal motility is associated with altered activities of membrane ion channels. Ion channels have important role in regulating membrane potential and cell excitability. This study was performed to investigate the effects of tamoxifen on the membrane ionic currents in colonic smooth muscle cells. METHODS: Murine colonic smooth muscle cells were isolated from the proximal colon using collagenase, and the membrane currents were recorded using a whole-cell patch clamp technique. RESULTS: Two types of voltage-dependent K+ currents were recorded (A-type and delayed rectifier K+ currents). Tamoxifen inhibited both types of voltage-dependent K+ currents in a dose-dependent manner. However, tamoxifen did not change the half-inactivation potential and the recovery time of voltage-dependent K+ currents. Chelerythrine, a protein kinase C inhibitor or phorbol 12, 13-dibutyrate, a protein kinase C activator did not affect the voltage-dependent K+ currents. Guanosine 5'-O-(2-thio-diphosphate) did not affect the tamoxifen-induced inhibition of voltage-dependent K+ currents. Tamoxifen inhibited voltage-dependent Ca2+ currents completely in whole-test ranges. CONCLUSIONS: These results suggest that tamoxifen can alter various membrane ionic currents in smooth muscle cells and cause some adverse effects on the gastrointestinal motility.
Animals
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Antineoplastic Agents, Hormonal/*pharmacology
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Calcium Channels/drug effects
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Colon/*drug effects/physiology
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English Abstract
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In Vitro
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Membrane Potentials
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Mice
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Myocytes, Smooth Muscle/*drug effects/physiology
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Potassium Channels/*drug effects
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Tamoxifen/*pharmacology
3.Methionine Enhances the Contractile Activity of Human Colon Circular Smooth Muscle In Vitro.
Eun Kyung CHOE ; Jung Sun MOON ; Kyu Joo PARK
Journal of Korean Medical Science 2012;27(7):777-783
Effective drug to manage constipation has been unsatisfactory. We sought to determine whether methionine has effect on the human colon. Human colon tissues were obtained from the specimens of colon resection. Microelectrode recording was performed and contractile activity of muscle strips and the propagation of the contractions in the colon segment were measured. At 10 microM, methionine depolarized the resting membrane potential (RMP) of circular muscle (CM) cells. In the CM strip, methionine increased the amplitude and area under the curve (AUC) of contractions. In the whole segment of colon, methionine increased the amplitude and AUC of the high amplitude contractions in the CM. These effects on contraction were maximal at 10 microM and were not observed in longitudinal muscles in both the strip and the colon segment. Methionine reversed the effects of pretreatment with sodium nitroprusside, tetrodotoxin and Nw-oxide-L-arginine, resulting in depolarization of the RMP, and increased amplitude and AUC of contractions in the muscle strip. Methionine treatment affected the wave pattern of the colon segment by evoking small sized amplitude contractions superimposed on preexisting wave patterns. Our results indicate that a compound mimicking methionine may provide prokinetic functions in the human colon.
Area Under Curve
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Arginine/pharmacology
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Colon/drug effects/physiology
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Humans
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Membrane Potentials/drug effects
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Methionine/*pharmacology
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Microelectrodes
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Muscle Contraction/*drug effects
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Muscle, Smooth/drug effects/*physiology
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Nitroprusside/pharmacology
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Tetrodotoxin/pharmacology
4.The Effect of Urocortin 1 on Motility in Isolated, Vascularly Perfused Rat Colon.
Il Young YOU ; Seungho LEE ; Ki Bae KIM ; Hee Seung LEE ; Jong Soon JANG ; Myeongho YEON ; Joung Ho HAN ; Soon Man YOON ; Hee Bok CHAE ; Seon Mee PARK ; Sei Jin YOUN
The Korean Journal of Gastroenterology 2015;65(5):283-290
BACKGROUND/AIMS: Urocortin 1, a corticotropin-releasing factor related peptide, increases colonic motility under stressful conditions. We investigated the effect of urocortin 1 on colonic motility using an experimental model with isolated rat colon in which the blood flow and intestinal nerves were preserved. Furthermore, we assessed whether this effect was mediated by adrenergic or cholinergic nerves. METHODS: Colonic motility was measured in the proximal and distal parts of resected rat colon. The colon resected from the peritoneum was stabilized, and then urocortin 1 (13.8, 138, 277, and 1,388 pM) was administered via a blood vessel. Motility index was measured in the last 5 min of the 15 min administration of urocortin 1 and expressed as percentage change from baseline. Subsequently, the change in motility was measured by perfusing urocortin 1 in colons pretreated with phentolamine, propranolol, hexamethonium, atropine, or tetrodotoxin. RESULTS: At concentrations of 13.8, 138, 277, and 1,388 pM, urocortin 1 increased the motility of proximal colon (20.4+/-7.2%, 48.4+/-20.9%, 67.0+/-25.8%, and 64.2+/-20.9%, respectively) and the motility of distal colon (3.3+/-3.3%, 7.8+/-7.8%, 71.1+/-28.6%, and 87.4+/-32.5%, respectively). The motility induced by urocortin 1 was significantly decreased by atropine to 2.4+/-2.4% in proximal colon and 3.4+/-3.4% in distal colon (p<0.05). However, tetrodotoxin, propranolol, phentolamine, and hexamethonium did not inhibit motility. CONCLUSIONS: Urocortin 1 increased colonic motility and it is considered that this effect was directly mediated by local muscarinic cholinergic receptors.
Animals
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Colon/*drug effects/physiology
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Injections, Intravenous
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Male
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Muscle Contraction/drug effects
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Neurotransmitter Agents/pharmacology
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Rats
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Rats, Sprague-Dawley
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Receptors, Cholinergic/chemistry/metabolism
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Urocortins/isolation & purification/*pharmacology
5.Effect of tongbian navel paste on colonic motility in children with constipation of slow transmission type.
Chinese Journal of Integrated Traditional and Western Medicine 2009;29(2):158-160
OBJECTIVETo observe the therapeutic effect of Tongbian Navel Paste (TBP, a self-formulated preparation consisting of both Chinese herbal and Western medicines) on children with constipation of slow transmission type (CSTT) and it influence on patients' colonic motility.
METHODSSixty-eight children with CSTT were randomly assigned to two groups, 38 in the treatment group treated with TBP, and 30 in the control group treated with oral taking Maren Zipi pill. The changes of clinical symptoms, and the outcomes of colon transmission test were observed and compared before and after treatment.
RESULTSColon transmission test showed the 48 h and 72 h barium discharging rate (%) in the treatment group before treatment was 10.1 +/- 3.2 and 46.2 +/- 3.9; after treatment, it raised to 59.9 +/- 4.1 and 73.6 +/- 3.6 respectively (P <0.05). The total effective rate in the treatment group was 89.47% and 73.33% in the control group, the difference between groups was significant (P<0.05).
CONCLUSIONTBP could promote the motility of colon, it is a safe, convenient and effective preparation for treatment of CSTT.
Administration, Cutaneous ; Adolescent ; Child ; Colon ; physiology ; Constipation ; drug therapy ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Gastrointestinal Motility ; drug effects ; Humans ; Male ; Phytotherapy
6.Stimulation of Cl- secretion by AlF4- and vanadate in T84 cells.
Tae Ho HWANG ; Jin Sup JUNG ; Hae Rahn BAE ; Il YUN ; Sang Ho LEE
Journal of Korean Medical Science 1994;9(6):497-504
We investigated the mechanism of Cl- secretion by fluoroaluminate(AlF4-) and sodium orthovanadate(vanadate) using the human colonic T84 cell line. T84 cell monolayers grown on collagen-coated filters were mounted in Ussing chambers to measure short circuit current(ISC). Serosal addition of AlF4- or vanadate to T84 monolayers produced a sustained increase in ISC. Removal of Ca2+ from the serosal bathing solution partially inhibited AlF4-(-)and vanadate-induced ISC, and readministration of Ca2+ restored AlF4-(-)and vanadate-induced ISC. Carbachol application in the presence of forskolin, AlF4- or vanadate induced a synergistic increase of ISC. Forskolin and vanadate significantly increased cellular cAMP level, while carbachol and AlF4- did not. Carbachol, AlF4- and vanadate significantly increased [Ca2+]i. After Na+ in mucosal bathing solution was replaced with K+, and the mucosal membrane of T84 cell was permeabilized with amphotericin B, AlF4-, vanadate, and carbachol increased K+ conductance, but forskolin did not. After sodium chloride in serosal bathing solution was replaced with sodium gluconate and the serosal membrane was permeabilized with nystatin, forskolin, AlF4-, and vanadate increased Cl- conductance, but carbachol did not. AlF4-(-)induced ISC was remarkably inhibited by the pretreatment of pertussis toxin(2 micrograms/ml) for 2 hours. These results indicate that AlF4- and vanadate can increase Cl- secretion via simultaneous stimulation of Cl- channel and K+ channel in T84 cells. However, the AlF4- action is mostly attributed to stimulation of pertussis toxin-sensitive G-proteins, whereas the vanadate action mostly results from G protein-independent mechanisms.
Aluminum/*pharmacology
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Amphotericin B/pharmacology
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Carbachol/pharmacology
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Cell Polarity
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Cells, Cultured/drug effects
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Chloride Channels/drug effects/*physiology
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Chlorides/*physiology
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Colon
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Electrophysiology
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Fluorine/*pharmacology
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Forskolin/pharmacology
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GTP-Binding Proteins/physiology
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Human
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Pertussis Toxin
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Potassium/pharmacology
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Potassium Channels/drug effects/physiology
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Second Messenger Systems
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Signal Transduction
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Support, Non-U.S. Gov't
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Vanadates/*pharmacology
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Virulence Factors, Bordetella/pharmacology
7.Store-operated Ca2+ channels in rat colonic smooth muscle cells.
Hua ZHOU ; De-Hu KONG ; Rong MA ; Dao-Ping KE ; Jin-Lan HU ; Jie SONG
Chinese Journal of Applied Physiology 2006;22(2):220-224
AIMTo study whether store-operated Ca2+ channel (SOC) is present in rat colonic smooth muscle cells.
METHODSIntracellular Ca2+ ([Ca2+]i) changes induced by thapsigargin- or caffeine-activated SOC channel were measured in enzymatically dissociated rat colonic smooth muscle cells with the fluorescent indicator Fura-2/AM.
RESULTSIn the absence of external Ca2+ , the sarco-endoplasmic reticulum Ca2+ pump inhibitor thapsigargin (1 micromol/L) and ryanodine receptor (RyR) activator caffeine both transiently elevated [Ca2+]i from (68.32 +/- 3.43) nmol/L to (240.85 +/- 12.65 ) nmol/L, (481.25 +/- 34.77) nmol/L. A subsequent reintroduction of Ca2+ into the extracellular solution resulted in [Ca2+]i further elevated to (457.55 +/- 19.80) nmol/L, (1005.93 +/- 54.62) nmol/L; (643.88 +/- 34.65) nmol/L, (920.16 +/- 43.25) nmol/L, respectively. And the elevated response was blocked by lanthanum (1 mmol/L), but was insensitive to L-type voltage calcium channels blocker verapamil and membrane depolarization.
CONCLUSIONSOC activated by store depletion are present in rat colonic smooth muscle cells. And we further prove the existence of such Ca2+ channels in excitable cells.
Animals ; Caffeine ; pharmacology ; Calcium ; metabolism ; Calcium Channels ; physiology ; Colon ; cytology ; Fura-2 ; metabolism ; Myocytes, Smooth Muscle ; drug effects ; metabolism ; Rats ; Rats, Wistar ; Thapsigargin ; pharmacology
8.Polymethoxylated flavonoids activate cystic fibrosis transmembrane conductance regulator chloride channel.
Huan-Huan CAO ; Fang FANG ; Bo YU ; Jian LUAN ; Yu JIANG ; Hong YANG
Acta Physiologica Sinica 2015;67(2):225-234
Cystic fibrosis transmembrane conductance regulator (CFTR), a cAMP-dependent chloride channel, plays key roles in fluid secretion in serous epithelial cells. Previously, we identified two polymethoxylated flavonoids, 3',4',5,5',6,7-hexamethoxyflavone (HMF) and 5-hydroxy-6,7,3',4'-tetramethoxyflavone (HTF) which could potentiate CFTR chloride channel activities. The present study was aimed to investigate the potentiation effects of HMF and HTF on CFTR Cl(-) channel activities by using a cell-based fluorescence assay and the short circuit Ussing chamber assay. The results of cell-based fluorescence assay showed that both HMF and HTF could dose-dependently potentiate CFTR Cl(-) channel activities in rapid and reversible ways, and the activations could be reversed by the CFTR blocker CFTRinh-172. Notably, HMF showed the highest affinity (EC50 = 2 μmol/L) to CFTR protein among the flavonoid CFTR activators identified so far. The activation of CFTR by HMF or HTF was forskolin (FSK) dependent. Both compounds showed additive effect with FSK and 3-Isobutyl-1-methylx (IBMX) in the activation of CFTR, while had no additive effect with genistein (GEN). In ex vivo studies, HMF and HTF could stimulate transepithelial Cl(-) secretion in rat colonic mucosa and enhance fluid secretion in mouse trachea submucosal glands. These results suggest that HMF and HTF may potentiate CFTR Cl(-) channel activities through both elevation of cAMP level and binding to CFTR protein pathways. The results provide new clues in elucidating structure and activity relationship of flavonoid CFTR activators. HMF might be developed as a new drug in the therapy of CFTR-related diseases such as bronchiectasis and habitual constipation.
Animals
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Colforsin
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Colon
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metabolism
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Cystic Fibrosis Transmembrane Conductance Regulator
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drug effects
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Flavones
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physiology
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Flavonoids
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pharmacology
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Genistein
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Intestinal Mucosa
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metabolism
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Mice
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Rats
9.Effect of emodin on motility signal transduction in colonic smooth muscle cells in rats with multiple organ dysfunction syndrome.
Zhe-Yu CHEN ; Qing-Hui QI ; Tao MA ; Xu JIAN
Chinese Journal of Integrated Traditional and Western Medicine 2004;24(12):1106-1109
OBJECTIVETo observe the effect of emodin on motility signal transduction and calcium ion in colonic smooth muscle cells (SMC) in rats with bacterial peritonitis caused multiple organ dysfunction syndrome (MODS).
METHODSObservation was conducted in colon of MODS model rats on (1) effects of emodin on the contraction of muscular strip and cells of colonic smooth muscle, and influences of specific myoglobulin light chain kinase inhibitor (ML-7) and selective proteinkinase C inhibitor (Calphostin C) on these effects; and (2) effect of emodin on calcium ion in SMC.
RESULTSEmodin could directly contract the muscular strip and cells of smooth muscle; ML-7 and Calphostine could inhibit these contractile action to some extent. Under MODS condition, emodin could still increase the intracellular calcium ion concentration; this effect could be inhibited by heparin (inosamine triphosphate receptor inhibitor IP3 and ryanodine receptor inhibitor in MODS model but the calcium chelator EGTA and nifedipine (the specific cell membrane voltage dependent calcium channel blocker) showed no influence on it.
CONCLUSIONEmodin could directly contract the colonic smooth muscle in MODS model rats, which is mediated by raise the signal path MLCK of calcium ion and the PKCa path for increase calcium sensibility. The mechanism of increasing calcium ion is mainly through IP3 and RyR the two calcium ion channel receptor in the sarcoplasm.
Animals ; Calcium ; metabolism ; Colon ; drug effects ; Emodin ; pharmacology ; Enzyme Inhibitors ; pharmacology ; Gastrointestinal Motility ; drug effects ; In Vitro Techniques ; Male ; Multiple Organ Failure ; physiopathology ; Muscle Contraction ; drug effects ; Muscle, Smooth ; cytology ; drug effects ; Myocytes, Smooth Muscle ; drug effects ; physiology ; Rats ; Rats, Wistar ; Signal Transduction
10.Effect of DA-9701 on Colorectal Distension-Induced Visceral Hypersensitivity in a Rat Model.
Eun Ran KIM ; Byung Hoon MIN ; Tae Ho LEE ; Miwon SON ; Poong Lyul RHEE
Gut and Liver 2014;8(4):388-393
BACKGROUND/AIMS: DA-9701 is a newly developed drug made from the vegetal extracts of Pharbitidis semen and Corydalis tuber. The aim of this study was to evaluate the effect of DA-9701 on colorectal distension (CRD)-induced visceral hypersensitivity in a rat model. METHODS: Male Sprague-Dawley rats were subjected to neonatal colon irritation (CI) using CRD at 1 week after birth (CI group). At 6 weeks after birth, CRD was applied to these rats with a pressure of 20 to 90 mm Hg, and changes in the mean arterial pressure (MAP) were measured at baseline (i.e., without any drug administration) and after the administration of different doses of DA-9701. RESULTS: In the absence of DA-9701, the MAP changes after CRD were significantly higher in the CI group than in the control group at all applied pressures. In the control group, MAP changes after CRD were not significantly affected by the administration of DA-9701. In the CI group, however, the administration of DA-9701 resulted in a significant decrease in MAP changes after CRD. The administration of DA-9701 at a dose of 1.0 mg/kg produced a more significant decrease in MAP changes than the 0.3 mg/kg dose. CONCLUSIONS: The administration of DA-9701 resulted in a significant increase in pain threshold in rats with CRD-induced visceral hypersensitivity.
Analgesics/administration & dosage/*pharmacology
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Animals
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Arterial Pressure/drug effects
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Colon, Descending/physiology
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Dilatation/methods
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Gastrointestinal Agents/administration & dosage/*pharmacology
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Male
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Pain Threshold/drug effects
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Plant Preparations/administration & dosage/*pharmacology
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Rats, Sprague-Dawley
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Visceral Pain/physiopathology/*prevention & control