• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.33-40
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• 2000

This study was designed to clarify the mechanism of the inhibitory action of a nitric oxide (NO) donor, 3-morpholino-sydnonimine (SIN-1), on contraction, cytosolic $Ca^{2+}$ level $([Ca^{2+}]_i)$ and ionic currents in guinea-pig ileum. SIN-1 $(0.01{\sim}100\;{\mu}M)$ inhibited 25 mM KCl- or histamine $(10\;{\mu}M)-induced$ contraction in a concentration-dependent manner. SIN-1 reduced both the 25 mM KCl- and the histamine-stimulated increases in muscle tension in parallel with decreased $[Ca^{2+}]_i.$ Using the patch clamp technique with a holding potential of -60 mV, SIN-1 $(10\;{\mu}M)$ decreased peak Ba currents $(I_{Ba})$ by $30.9{\pm}5.4%$ (n=6) when voltage was stepped from -60 mV to +10 mV and this effect was blocked by ODQ $(1\;{\mu}M),$ a soluble guanylyl cyclase inhibitor. Cu/Zn SOD (100 U/ml), the free radical scavenger, had little effect on basal $I_{Ba},$ and SIN-1 $(10\;{\mu}M)$ inhibited peak $I_{Ba}$ by $32.4{\pm}5.8%$ (n=5) in the presence of Cu/Zn SOD. In a cell clamped at a holding-potential of -40 mV, application of $10\;{\mu}M$ histamine induced an inward current. The histamine-induced inward current was markedly and reversibly inhibited by $10\;{\mu}M$ SIN-1, and this effect was abolished by ODQ $(1\;{\mu}M).$ In addition, SIN-1 markedly increased the depolarization-activated outward $K^+$ currents in the all potential ranges. We concluded that SIN-1 inhibits smooth muscle contraction mainly by decreasing $[Ca^{2+}]_i$ resulted from the inhibition of L-type $Ca^{2+}$ channels and the inhibition of nonselective cation currents and/or by the activation of $K^+$ currents via a cGMP-dependent pathway.

• 대한약리학회지
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• 제14권1_2호
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• pp.33-40
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• 1978

1. guinea-pig 요관(尿管) 평골근(平滑筋)의 수축(收縮) 및 이완반응(弛緩反應) 연령이 증가(增加)에 의(依)하여 크게 영향(影響)을 받는다는 사실(事實)을 관찰(觀察)하였다. 2. 2-3주, 3개월 및 2-3년 guinea-pig 요관(尿管)을 적출하고 Tyrode 액내(液內)에서 train stimulation법(法)으로 일정(一定)하게 수축반응(收縮反應)을 일으킨다. 3. $Ca^{++}$-free Tyrode 액(液)에서 전기자극(電氣刺戟) 반응(反應)이 소실(消失)된 후(後) $Ca^{++}$ 함유(含有) Tyrode 액(液)을 가(加)하여 야기(惹起)되는 수축반응(收縮反應)의 회복(恢復)에는 3개월(個月) 및 2-3년(年) 요관(尿管)에 비(比)하여 2-3주(週) 요관(尿管)은 훨씬 낮은 농도(濃度)의 $Ca^{++}$을 필요(必要)로 하였으며 비록 2.7mM $Ca^{++}$을 가(加)하여도 2-3주(週) 및 3개월(個月) 요관에 있어서는 처음 수축고의 90% 이상을 회복하였으나 2-3년(年) 요관(尿管)에서는 77.2%만 회복하였다. 4. ISP는 2-3년 요관(尿管)에 비(比)하여 2-3주(適) 요관(尿管)에 있어서 수축고의 억제(抑制) 효과(效果)가 유의(有意)하게 강(强)하였고 theophylline은 연령(年齡)에 관계없이 양군(兩群)모두 강력(强力)히 억제작용(抑制作用)을 나타내었다. 5. 2-3주 뇨관의 수축에 대하여 dibutyryl cyclic AMP는 dose-dependent하게 억제를 나타내었으나 2-3년 노요관(老尿管)에 있어서는 이와같은 현상은 없었다. 그리고 요관(尿管)조직내 cyclic AMP 함량(含量)은 2주기니픽 뇨관에서는 17개월 뇨관에 비(比)하여 73%의 높은 농도를 나타내었고 cyclic GMP의 함량(含量)은 큰 차이를 볼 수 없었다. 6. 유년(幼年) 요관평골근(尿管平滑筋)은 노요관(老尿管)에 비(比)하여 근수축(筋收縮) 및 이완(弛緩)에 관여(關與)하는 $Ca^{++}$의 동원(動員) 및 저장(貯藏)에 있어서 높은 효율성(效率性)을 가지고 있다고 사료(思料)되는 바이다.

• 동의생리병리학회지
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• 제27권4호
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• pp.400-408
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• 2013

This study aimed to investigate the relaxation effects and its underlying mechanisms of Rubus coreanus(RC) extract in contracted rabbit corpus cavernous tissues by phenylephrine(PE) $1{\mu}M$. In order to define the relaxation effects of RC, rabbit corpus cavernous tissues were prepared in $2{\times}2{\times}6mm$ sized strip. The dose-dependent relaxation responses of RC at 0.01-3.0 $mg/m{\ell}$ in contracted strips induced by PE were measured and also observed after endothelial denudation. To analyze the underlying mechanisms of RC-induced relaxation, indomethacin(IM), tetraethylammonium chloride(TEA), $N{\omega}$-nitro-L-arginine (L-NNA), methylene blue(MB) were treated before RC extract infused into precontracted strips induced by PE. To study the effect of RC extract on influx of extracellular $Ca^{2+}$ in corpus cavernous strips, calcium chloride(Ca) 1 mM infused into precontracted strips induced by PE after pretreatment of RC extract in $Ca^{2+}$-free krebs-ringer solution. To investigate cytotoxic activity and nitric oxide(NO) concentration of RC extract on human umbilical vein endothelial cell(HUVEC), cell viability on HUVEC was measured by MTT assay, and NO concentration was measured by Griess reagent system. The cavernous strips were significantly relaxed by RC extract at 1.0 $mg/m{\ell}$, 3.0 $mg/m{\ell}$ and the relaxation responses to RC were inhibited significantly by endothelial disruption. The pretreatment of IM, TEA didn't affect RC extract-induced endothelium-dependent relaxation, but the pretreatment of L-NNA, MB reduced RC extract-induced endothelium-dependent relaxation. When $Ca^{2+}$ was supplied the cavernous strips which were precontracted by PE in a $Ca^{2+}$-free krebs-ringer solution, contraction of strips was increased, but pretreatment of RC inhibited contractile response to $Ca^{2+}$. When RC extract was applicated on HUVEC, NO concentration was increased. Our findings show that RC extract exerts a relaxing effect on corpus cavernosum in part by suppressing influx of extracellular $Ca^{2+}$ through activating the NO-cGMP system.

• Biomolecules & Therapeutics
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• 제16권3호
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• pp.249-254
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• 2008

The present study was undertaken to determine whether hypoxia influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Hypoxia significantly inhibited fluoride-induced contraction regardless of endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction suggesting that other pathway such as $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, hypoxia significantly decreased fluoride-induced increase of phospho-myosin-targeting subunit of myosin light chain phosphatase (pMYPT1). Interestingly, hypoxia didn't inhibit significantly phenylephrine-induced contraction suggesting that myosin light chain kinase (MLCK) activity or thin filament regulation is less important on the hypoxia-induced vasorelaxation in the denuded muscle than Rho-kinase activity. In conclusion, this study provides the evidence and possible related mechanism concerning the vasodilation effect of hypoxia on the agonist-specific contraction in rat aortic rings regardless of endothelial function.

• 대한한방내과학회지
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• 제11권1호
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• pp.15-27
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• 1990

For the purpose of examing on the efficancy of the Boolwhangumjeonggisan and on the effect of the Boolwhangumjeonggisan, dropsy animals given water boil ding abstraction exgis power. What made an experiment, the motility of isolate ileume, anticathartic action, the action of gastric juice, tied pylous ulcer and inhibited vomitting. 1. Boolwhangumjeonggisan displayed great suppresion effect in regard to automatic movement of the motility of isolated of mice and displayed anti-acethylcholine action, antibarium chloride action. Thus, the origin of muscle relaxation for internal smooth muscle is admitted. 2. It displayed great rexation effect in regard to fraction of rat's stomach and displayed contentional effect in regard to a cetylcholine and barium chloride. 3. It decreased rat of barium sulfate transport through the small intestine of mice. 4. It recognized anti-cathartic action, rat suffered from leading diarrhea by caster oil. 5. Total activity, pepsin secretion decreased and increased the pH of stomach in Shay's method. 6. It recognized powerful prevention effect on tied pylous ulcer. 7. It inhibited vomitting by administration of CuSo4 in frog.

• Biomolecules & Therapeutics
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• 제20권3호
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• pp.352-356
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• 2012

The present study was undertaken to determine whether ethanol influences on the agonist-induced vascular smooth muscle contraction and, if so, to investigate the related mechanism. The measurement of isometric contractions using a computerized data acquisition system was combined with molecular experiments. Ethanol significantly inhibited thromboxane $A_2$ mimetic-induced contraction with intact endothelial function, but there was no relaxation on thromboxane $A_2$ mimetic U-46619-induced contraction irrespective of endothelium suggesting that the pathway such as Rho-kinase activation, $Ca^{2+}$ entry or thin filament regulation was not affected. In addition, ethanol didn't decrease thromboxane $A_2$ mimetic-induced increase of phospho-myosin phosphatase targeting subunit protein 1 (pMYPT1) or pERK1/2. Interestingly, ethanol didn't inhibit significantly phorbol ester-induced contraction in denuded muscles suggesting that thin filament regulation is less important on the ethanol-induced regulation in the muscle than endothelial NO synthesis. In conclusion, this study provides the evidence and possible related mechanism concerning the effect of ethanol on the agonist-dependent contraction in rat aortic rings with regard to endothelial function.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1997년도 추계학술대회
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• pp.41-46
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• 1997

Lower esophageal sphincter (LES) is characterized by the ability to maintain a sustained pressure, and to relax allowing the passage of a bolus, whereas the esophagus is normally relaxed and contracts only briefly when required to produce peristalsis (fig. 1). The neuromuscular mechanisms that participate in the physiological regulation of these functions are not well understood, but it is thought that LES tone is spontaneous and regulated mostly through myogenic mechanisms, whereas LES relaxation and esophageal contraction are induced by neural mechanisms. Gastroesophageal reflux represents the effortless movement of gastric contents from stomach to esophagus. Because this phenomenon occurs in virtually everyone multiple times every day and in the majority of people without clinical consequences, the reflux per se is not disease. However in some cases, it can be pathologic, producing symptoms and signs called gastroesophageal reflux disease (GERD), which mechanism is not well known. It may result in heart burn, chronic esophagitis, aspiration pneumonia, esophageal strictures, and Barrett's esophagus.

• The Korean Journal of Physiology and Pharmacology
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• 제17권1호
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• pp.31-36
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• 2013

The present study was undertaken to investigate the influence of eupatilin on vascular smooth muscle contractility and to determine the mechanism involved. Denuded aortic rings from male rats were used and isometric contractions were recorded and combined with molecular experiments. Eupatilin more significantly relaxed fluoride-induced vascular contraction than thromboxane $A_2$ or phorbol ester-induced contraction suggesting as a possible anti-hypertensive on the agonist-induced vascular contraction regardless of endothelial nitric oxide synthesis. Furthermore, eupatilin significantly inhibited fluoride-induced increases in pMYPT1 levels. On the other hand, it didn't significantly inhibit phorbol ester-induced increases in pERK1/2 levels suggesting the mechanism involving the primarily inhibition of Rho-kinase activity and the subsequent phosphorylation of MYPT1. This study provides evidence regarding the mechanism underlying the relaxation effect of eupatilin on agonist-induced vascular contraction regardless of endothelial function.

• 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.250.2-251
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• 2002

DA-8159 is a new. highly selective. potent cyclic-GMP phosphodiesterase 5 inhibitor developed by Dong-A Pharmaceutical Company(Kyunggi, Korea) as an oral drug for the treatment of erectile dysfunction. NO- cGMP signal transduction pathway plays a key role for relaxation of corpus cavernosal smooth muscle. In this study. the efficacy of DA-8159 was evaluated by measuring the length of uncovered penile mucosa in spinal cord injury(SCI) rabbits. (omitted)

• 사상체질의학회지
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• 제5권1호
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• pp.157-173
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• 1993

In order to investigate experimentally the clinical effects of Soeuminsohaphyangwon that was prescribed to cure the Wisunanrihanbyung of Soeum-In, the author experimented various activities of mixed extract from the Soeuminsohaphyangwon by the method prescribed in the experimental part. The results of the studies were summerized as follows : 1. Suppressive action was not shown on the convulsion induced by strychnine but significant effect was noted on the convulsion induced by picrotoxin and caffeine. 2. In acetic acid method experiment analgesic effect was noted. 3. A prolongation of anesthetic time by Pentobarbital sodium and antipyretic effect was observed. 4. Relaxing action was noted on the ileums of mice, also same effect was recognized on contraction of the ileums due to acetylcholine, barium chloride and histamine 2 HCl. 5. The expansion of blood vessels by relaxation of smooth muscle and fall of blood pressure were noted. According to the above results, effects based on oriental medical references were approximate to the actual experimental results.