• 대한약학회:학술대회논문집
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• 대한약학회 2002년도 Proceedings of the Convention of the Pharmaceutical Society of Korea Vol.2
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• pp.242.1-242.1
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• 2002

H$_2$O$_2$ has been shown to act as a signaling molecule involved in many cellular functions such as oxidant-induced stress, apoptosis, proliferation. In this study, we investigated the action mechanisms of H$_2$O$_2$ on activation of Extracellular Signal-Regulated Protein Kinase(ERK) in cultured feline ileal smooth muscle cells(ISMC). Western blot analysis done with phospho-specific MAP kinases antibodies demonstrated that potent activation of ERK and moderate activation of SAPK/JNK occurred within 30 min of H$_2$O$_2$ treatment. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• 제2권2호
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• pp.225-232
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• 1998

To investigate the possible involvement of outward potassium ($K^+$) currents in nitric oxide-induced relaxation in intestinal smooth muscle, we used whole-cell patch clamp technique in freshly dispersed guinea-pig ileum longitudinal smooth muscle cells. When cells were held at -60 mV and depolarized from -40 mV to -50 mV in 10 mV increments, sustained outward $K^+$ currents were evoked. The outward $K^+$ currents were markedly increased by the addition of 10 ${\mu}M$ sodium nitroprusside (SNP). 10 ${\mu}M$ S-nitroso-N-acetylpenicillamine (SNAP) and 1 mM 8-Bromo-cyclic GMP (8-Br-cGMP) also showed a similar effect to that of SNP. 1 mM tetraethylammonium (TEA) significantly reduced depolarization-activated outward $K^+$ currents. SNP-enhanced outward $K^+$ currents were blocked by the application of TEA. High EGTA containing pipette solution (10 mM) reduced the control currents and also inhibited the SNP-enhanced outward $K^+$ currents. 5 mM 4-aminopyridine (4-AP) significantly reduced the control currents but showed no effect on SNP-enhanced outward $K^+$ currents. 0.3 ${\mu}M$ apamin and 10 ${\mu}M$ glibenclamide showed no effect on SNP-enhanced outward $K^+$ currents. 10 ${\mu}M$ 1H-[1,2,4]oxadiazolo [4,3-a]quinoxaline-1-one (ODQ), a specific inhibitor of soluble guanylate cyclase, significantly blocked SNP-enhanced $K^+$ currents. We conclude that NO donors activate the $Ca^{2+}-activated$ $K^+$ channels in guinea-pig ileal smooth muscle via activation of guanylate cyclase.

• The Korean Journal of Physiology and Pharmacology
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• 제8권6호
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• pp.339-344
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• 2004

Recent data have shown the importance of oxidative stresses in the pathogenesis of inflammatory bowel disease, crohn's disease and ulcerative colitis. $H_2O_2$, reactive oxygen species (ROS) donor, has been reported to act as a signaling molecule involved in a variety of cellular functions such as apo/ptosis and proliferation. In the present study, we investigated viability of cultured ileal smooth muscle cells (ISMC) after stimulation with $H_2O_2$. Trypan blue method revealed that the cell viability of ISMC treated with 1 mM $H_2O_2$ was not different from that of controls at up to 2 h time point, while treatment of ISMC with 1 mM $H_2O_2$ for 48 h finally induced significant decrease in the cell viability. Therefore, we evaluated whether $H_2O_2$ was capable of ERKs activation in ISMC for the short-term exposure and examined whether tyrosine kinase was involved in the process of ERK activation by $H_2O_2$ in ISMC. We also investigated the effects of $H_2O_2$ on activation of SAPK/JNK and p38 MAP kinase in ISMC. Thus, ISMC were cultured and exposed to $H_2O_2$, and western blot analysis was performed with phosphospecific MAP kinase antibodies. Robust activation of ERK occurred within 30 min of 1 mM $H_2O_2$ treatment. $H_2O_2-induced$ ERK activation was attenuated by a tyrosine kinase inhibitor, genistein, indicating that tyrosine kinase was probably involved in the ERK activation by $H_2O_2$. $H_2O_2$ was a moderate activator of SAPK/JNK, while p38 MAP kinase was not activated by $H_2O_2$. We suggest that ERK activation induced by short-term $H_2O_2$ treatment plays a critical role in cellular protection in the early stage of response to oxidative stress. The present study suggests the necessity of identification of MAPK signaling pathways affected by ROS, since it could ultimately elucidate cellular consequences involved in initiation and perpetuation of intestinal tissue damage in the diseases such as crohn's disease and ulcerative colitis, resulted from excessive ROS.

• 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.

• Journal of Yeungnam Medical Science
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• 제6권2호
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• pp.13-22
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• 1989

Benzodiazepine 계통의 약물들은 진정, 최면제로 진정, 최면, 불안의 감소와 함께 횡문근 이완과 항 경련 작용을 가진다는 것은 이미 잘 알려진 바이나 이러한 약리 작용의 기전에 대해서는 아직 확실하게 밝혀진 바가 없다. 최근 이러한 약리 작용과 연관성을 지니는 것으로 알려진 뇌내의 benzodiazepine의 수용체(receptor)를 통한 자극 전달 기전에 calcium 이온의 역할이 큰 비중을 차지할 수 있음이 대두되었다. 또 뇌 이외의 다수의 말초 조직에서도 benzodiazepine의 수용체가 있으며, 이들도 calcium 이온과 상호 작용 할 것이라고 보고된 바가 있으나 이들의 약리 작용과 그 작용 기전에 대해서는 아직 확실히 밝혀진 바가 없다. 이에 저자는 benzodiazepine 계통 약물 중 대표적이라 할 수 있는 diazepam을 사용하여 diazepam이 장관 평활근의 수축성에 미치는 영향을 calcium 이온과 연관시켜 검색하기 위하여 흰쥐 회장 평활근에서 적출한 종주근 절편을 적출 근편 실험조내에서 diazepam 처치 전후의 carbachol, histamine 및 calcium 유발 수축성의 변화를 등척성 장력 측정기를 사용하여 관찰하여 다음과 같은 결과를 얻었다. 1. Diazepam은 흰쥐 회장 절편의 기본 장력을 농도 의존적으로 감소시켰다. 2. Diazepam은 흰쥐 회장 절편의 carbachol-유발 수축 작용을 고농도에서는 억제시켰으며 저농도에서는 오히려 증강시키는 이중 효과를 나타내었다. 3. Diazepam 존재하에서 흰쥐 회장 절편의 histamine-유발 수축 작용은 억제되었으며, diazepam의 농도가 증가함에 따라 그 억제도는 증가하였다. 4. 칼슘 배제 용액에서 칼슘 재 투여로 인한 회장 절편의 장력의 회복율은 diazepam 전처치에 의해 억제되었으며, diazepam의 농도가 증가함에 따라 그 억제도는 증가하였다. 이상의 실험 결과로 미루어 diazepam은 흰쥐 회장 종주근의 수축성을 억제시키며 이 작용은 diazepam이 평활근 세포내로의 calcium의 유입을 억제함으로써 나타나는 것으로 사료된다.