• The Korean Journal of Physiology and Pharmacology
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• v.12 no.3
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• pp.111-115
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• 2008

The effects of (-)-epigallocatechin gallate (EGCG) on pacemaker activities of cultured interstitial cells of Cajal (ICC) from murine small intestine were investigated using whole-cell patch-clamp technique at $30^{\circ}C$ and $Ca^{2+}$ image analysis. ICC generated spontaneous pacemaker currents at a holding potential of -70 mV. The treatment of ICC with EGCG resulted in a dose-dependent decrease in the frequency and amplitude of pacemaker currents. SQ-22536, an adenylate cyclase inhibitor, and ODQ, a guanylate cyclase inhibitor, did not inhibit the effects of EGCG. EGCG-induced effects on pacemaker currents were not inhibited by glibenclamide, an ATP-sensitive $K^+$ channel blocker and TEA, a $Ca^{2+}$-activated $K^+$ channel blocker. Also, we found that EGCG inhibited the spontaneous $[Ca^{2+}]_i$ oscillations in cultured ICC. In conclusion, EGCG inhibited the pacemaker activity of ICC and reduced $[Ca^{2+}]_i$ oscillations by cAMP-, cGMP-, ATP-sensitive $K^+$ channel-independent manner.

• Journal of Physiology & Pathology in Korean Medicine
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• v.25 no.4
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• pp.603-607
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• 2011

The purpose of this study is to investigate the effects of Carthami Flos on interstitial cells of Cajal in the gastrointestinal tract. Many regions of the tunica muscularis of the gastrointestinal (GI) tract display spontaneous contraction. These spontaneous contractions are mediated by periodic generation of electrical slow waves. Recent studies have shown that the interstitial cells of Cajal (ICCs) act as pacemakers and conductors of electrical slow waves in gastrointestinal smooth muscles. We investigated the cytotoxicity activity, antioxidant activity, and pacemaking activity. The cytotoxicity activity was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assay. Antioxidant activities were determined by DPPH (1.1-diphenyl-2-picrylhydrazyl) radical scavenging capacity assay and DCFH-DA (2,7-dichlorofluorescein diacetate) method. The effects of Carthami Flos on the pacemaker potentials in cultured ICCs from murine small intestine were investigated by using whole-cell patch-clamp techniques at $30^{\circ}C$. The addition of Carthami Flos (5, 10, $30{\mu}g$/ml) depolarized the resting membrane potentials in a concentration dependent manner. These results suggest that the GI tract can be targets for Carthami Flos, and their interaction can affect intestinal motility.

• Journal of Pharmaceutical Investigation
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• v.37 no.6
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• pp.339-347
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• 2007

SMEDDS is mixture of oils, surfactants, and cosurfactants, which are emulsified in aqueous media under conditions of gentle agitation and digestive motility that would be encountered in the gastro-intestinal(GI) tract. The main purpose of this work is to prepare self-microemulsifying drug delivery system(SMEDDS) for oral bioavailability enhancement of a poorly water soluble drug, atorvastatin calcium. Solubility of atorvastatin calcium was determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identity the efficient self-emulsification region and particle size distributions of the resultant micro emulsions were determined using a laser diffraction sizer. Optimized formulations for in vitro dissolution and bioavailability assessment were $Capryol^{(R)}$ 90(50%), Tetraglycol(16%), and $Cremophor^{(R)}$ EL(32%). The release rate of atorvastatin from SMEDDS was significantly higher than the conventional tablet ($Lipitor^{(R)}$), 2-fold. Our studies illustrated the potential use of SMEDDS for the delivery of hydrophobic compounds, such as atorvastatin calcium by the oral route.

• The Korean Journal of Physiology and Pharmacology
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• v.11 no.1
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• pp.15-20
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• 2007

To investigate whether hydrogen peroxide($H_2O_2$) affects intestinal motility, pacemaker currents and membrane potential were recorded in cultured interstitial cells of Cajal(ICC) from murine small intestine by using a whole-cell patch clamp. In whole cell patch technique at $30^{\circ}C$, ICC generated spontaneous pacemaker potential under current clamp mode(I=0) and inward currents(pacemaker currents) under voltage clamp mode at a holding potential of -70 mV. When ICC were treated with $H_2O_2$ in ICC, $H_2O_2$ hyperpolarized the membrane potential under currents clamp mode and decreased both the frequency and amplitude of pacemaker currents and increased the resting currents in outward direction under voltage clamp mode. Also, $H_2O_2$ inhibited the pacemaker currents in a dose-dependent manner. Because the properties of $H_2O_2$ action on pacemaker currents were same as the effects of pinacidil(ATP-sensitive $K^+$ channels opener), we tested the effects of glibenclamide(ATP-sensitive $K^+$ channels blocker) on $H_2O_2$ action in ICC, and found that the effects of $H_2O_2$ on pacemaker currents were blocked by co- or pre- treatment of glibenclamide. These results suggest that $H_2O_2$ inhibits pacemaker currents of ICC by activating ATP-sensitive $K^+$ channels.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.271-277
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• 1999

Safety evaluation of LB71350, a new HIV-1 protease inhibitor, was performed in mice, rats and dogs. For the general behavior of mice, LB71350 at an oral dose of 200 mg/kg did not show any significant effects on muscle tone and locomotor activity. In terms of central nervous system, at oral doses of 200 mg/kg and 1000 mg/kg, LB71350 inhibited acetic acid-induced pain response approximately 41% and 83% of control. respectively. At oral doses of 200 mg/kg and 500 mg/kg, it reduced the rectal body temperature in rats. Pentylenetetrazole-induced seizure in mice was slightly potentiated by oral administration of LB71350 at doses ranging from 200 mg/kg to 1000 mg/Ag. Single or five day treatment of LB71350 doubled the hexobarbital- induced sleeping time in mice at oral doses ranging from 50 mg/kg to 500 mg/kg. It did not cause any effects on gastric secretion and acidity in rat at oral doses of 200 mg/kg and 1000 mg/kg and also it did not change intestinal motility in mice up to 1000 mg/kg. Blood coagulation indices such as prothrombin time (PT), activated partial thromboplastin time (aPTT), and thrombin time (TT) in rats were not affected by the treatment of LB71350 up to 500 mg/kg. LB71350 caused no significant effects on the cardiac output, stroke volume, heart rate, and mean blood pressure when infused intravenously to the anesthetized rats and dogs. Taken together, LB71350 at high oral doses caused significant pharmacological effects on the central nervous system and the hexobarbital-induced sleeping time.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.30 no.2
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• pp.244-251
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• 1997

The relationship between structure and biological activity was studied on the three neuropeptides (mammalian, trout- and goldfish-neuropeptide $\gamma$) that were syntheized by the solid-phase method. Circular dichroism spectra showed that mammalian, trout- and goldfish-neuropeptide $\gamma$ adopted an unordered structure in buffer solution. In the-presence of neutral and acidic liposomes, mammalian and trout-neuropeptioe $\gamma$ also took a random structure. However, goldfish-neuropeptide $\gamma$ took an $\alpha-helical$ structure in acidic liposomes. The intestinal motility response was investigated with carp intestines, guinea-pig ileums and rat duodenums. In case of carp intestine, contractile activity was as follows : goldfish-neuropeptide $\gamma\simeq$ trout-neuropeptide $\gamma>$ mammalian-neuropeptide $\gamma$, On the other hand, the contractile activity of mammalian-neuropeptide $\gamma$ was more potent than trout- and goldfish-neuropeptide $\gamma$ in the guinea-pig ileums and rat duodenums. These results suggest that neuropeptide $\gamma$ show the species-specific activity.

• Korean Journal of Acupuncture
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• v.25 no.3
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• pp.147-166
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• 2008

Objectives : Crohn's disease (CD) is characterized by a chronic relapsing inflammation of the bowel in which proinflammatory cytokines play an important perpetuating role. Methods : Mice (preventive animal model of gliotoxin) were treated with 5 % 2,4,6-trinitrobenzenesulfonic acid (TNBS) at day 1 and day 7. To investigate preventive effects of acupuncture with Gujin at $LI_{11}$, acupuncture was carried out at day -1, day 1, day 3. And, to investigate therapeutic effects, acupuncture with Gujin was carried out at day 3, day 5, day 7. For the data analysis, we checked weight and width of colon, diarrhea, edema, survival rate, changes of body weight, and myeloperoxygenase (MPO) activity. For analysing protein expression, we carried out immunohistochemical staining and Western blot and we analyzed mRNA expression by RT-PCR. Results : Colon of TNBS treated mice was erosive and shortening compared with the colon of control mice and induced damages of colon epithelial cell layer and induced infiltration of immune cells in all layer of colon. Acupuncture of gujin at $LI_{11}$ in preventive mode suppressed macorscopic damages such as erosive and shortening of colon by TNBS and damages of intestinal epithelial cells and infiltration of immune cells in the colon. The average weight of 5 cm distal colon was increased in TNBS treated mice (758${\mu}g$) compared with in control mice (112${\mu}g$) and width of distal colon was also increased in TNBS treated mice (4.9mm) compared with in control mice (1.3mm). Acupuncture with Gujin at $LI_{11}$ in preventive and therapeutic mode suppressed increase of colon weight and width by TNBS. TNBS induced edema of colon and diarrhea and Acupunctured with Gujin at $LI_{11}$ in preventive and therapeutic mode ameliorated these symptom by TNBS. In preventive and therapeutic mode, the effects of acupuncture with Gujin at $LI_{11}$ were increasing the motility, suppressing body weight decreasing, suppressing MPO activity, reducing expressing of TNF-${\alpha}$, IL-1b, and ICAM-1 in colon compared with that by TNBS Conclusions : This study demonstrates that acupuncture with Gujin at $LI_{11}$ represents a potential therapeutic method of Crohn's disease.

• The Korean Journal of Physiology and Pharmacology
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• v.15 no.3
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• pp.129-135
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• 2011

In this study we determined whether or not 5-hydroxytryptamine (5-HT) has an effect on the pacemaker activities of interstitial cells of Cajal (ICC) from the mouse small intestine. The actions of 5-HT on pacemaker activities were investigated using a whole-cell patch-clamp technique, intracellular $Ca^{2+}$ ($[Ca^{2+}]_i$) analysis, and RT-PCR in ICC. Exogenously-treated 5-HT showed tonic inward currents on pacemaker currents in ICC under the voltage-clamp mode in a dose-dependent manner. Based on RT-PCR results, we found the existence of 5-$HT_{2B,\;3,\;4,\;and\;7}$ receptors in ICC. However, SDZ 205557 (a 5-$HT_4$ receptor antagonist), SB 269970 (a 5-$HT_7$ receptor antagonist), 3-tropanylindole - 3 - carboxylate methiodide (3-TCM; a 5-$HT_3$ antagonist) blocked the 5-HT-induced action on pacemaker activity, but not SB 204741 (a 5-$HT_{2B}$ receptor antagonist). Based on $[Ca^{2+}]_i$ analysis, we found that 5-HT increased the intensity of $[Ca^{2+}]_i$. The treatment of PD 98059 or JNK II inhibitor blocked the 5-HT-induced action on pacemaker activity of ICC, but not SB 203580. In summary, these results suggest that 5-HT can modulate pacemaker activity through 5-$HT_{3,\;4,\;and\;7}$ receptors via $[Ca^{2+}]_i$ mobilization and regulation of mitogen-activated protein kinases.

• The Korean Journal of Physiology
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• v.20 no.2
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• pp.192-198
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• 1986

The present study was undertaken to see an interaction of dopamine and cholecystokinin on spontaneous contractility of the small intestine including the duodenal bulb. A possible neural mechanism of the interaction was alto examined. The spontaneous isometric contractility of a segment of the duodenal bulb, duodenum, jejunum and ileum obtained from the rabbit anesthetized with ether was recorded in a chamber filled with Krebs-Ringer's solution. The solution was constantly kept at $37^{\circ}C$ and aerated with $O_2$ containing 5% $CO_2$. After 20 min from beginning of the contraction, dopamine $(10^{-4}M)$, CCK-8($10^{-8}M$), domperidone($10^{-5}M$) and tetrodotoxin ($10^{-6}M$) were administered into the chamber The following results were obtained by analyzing changes in the contractility of the intestinal segments. 1) Dopamine inhibited the spontaneous contractility of the duodenal bulb, duodenum, jejunum and ileum. The inhibitory action of dopamine on all parts of the small intestine except the ileum was reduced by tetrodotoxin. 2) Domperidone knwon to be a specific peripheral dopamine receptor antagonist blocked the inhibitory action of dopamine on all parts of the small intestine. The antagonistic action of domperidone on all parts of the small intestine except the ileum was completely abolished by tetrodotoxin. 3) CCK-8 reduced the inhibitory action of dopamine on all parts of the small intestine. The effect of CCK-8 on the dopamine action was diminished by tetrodotoxin. These results suggest that dopamine inhibits the spontaneous contractility of the small intestine including the duodenal bulb and CCK-8 reduces the inhibitory action of dopamine through the enteric nervous system.

• Korean Journal of Fisheries and Aquatic Sciences
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• v.32 no.2
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• pp.232-237
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• 1999

The relationship between structure and contractile activity was studied on the three neuropeptide $\gamma$ (mammalian-, bowfin-, shark-NP$\gamma$) that were synthesized by the solid-phase method. Circular dichroism spectra showed that mammalian-, bowfin- and shark-neuropeptide $\gamma$ took an unordered structure in buffer solution and artificial liposome. The intestinal motility response was investigated with guinea-pig ileum, rat duodenum and carp intestine. In case of carp intestine, contractile activity was as follows; bowfin-NP$\gamma$> shark-NP$\gamma$>mammalian-NP$\gamma$, On the other hand, the contractile activity of mammalian-neuropeptide $\gamma$ was more potent than those of bowfin-, shark-neuropeptide $\gamma$ in the guinea-pig ileum and rat duodenum. These results suggest that NP$\gamma$ show the species-specific activity.