• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.37-37
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• 1992

세포의 흥분성과 막전위의 조절에 있어서 $K^{+}$ channel의 역할이 크다는 사실이 인정 됨으로서 (Rudy, 1988) $K^{+}$ channel 개방 약물의 약리학적 연구와 임상적 응용에 대한 관심은 높아졌다. Cromakalim, nicorandil 및 pinacidil등이 혈관 평활근을 특히 예민하게 이완시킨다. 작용기전으로서는 세포의 원형질 막을 통한 $K^{+}$ 전도의 항진과 $K^{+}$ outward current의 증가가 막 과분극을 일으킨다. 이러한 결과는 막흥분에 의한 voltage-dependent $Ca^{++}$ channel을 닫게하고 세포내 free $Ca^{++}$의 농도를 감소시켜 혈관의 흥분성과 수축력의 감소를 야기하여 근이완을 야기한다. 한편, 평활근 세포막의 $Na^{+}$-$K^{+}$ ATPase도 활성화하면 electrogenic pump를 가동하여 막 과분극을 일으키고 막 흥분성을 저하시킨다. $Na^{+}$-$K^{+}$ pump는 세포 바깥의 $K^{+}$과 세포안의 $Na^{+}$농도에 의하여 활성화한다.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1992.05a
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• pp.27-27
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• 1992

많은 홀몬, 성장인자 및 신경 전달물질들은 각각에 대한 세포막의 수용체와 결합하여 Phospholipase C (PLC)를 활성화시키므로서 신호를 세포내로 전달하여 세포의 성장, 대사, 신경 흥분, 수축 및 분비 등의 생리 현상을 나타내고 있다. 이 신호 전달의 중심 효소인 PLC는 현재까지의 효소 분리, 유전자 클로닝 등의 방법으로 3가지 Class에 적어도 8종유의 등위효소(Isozyme)들이 존재하고 있는 것으로 밝혀지고 있다. 본 연구에서는 이와 같은 등위효소에 특이적인 조절 물질을 선별할 수 있는 체계를 확립하기 위하여 새로운 동위효소의 분리 및 규명과 이 동위효소들에 대한 과발현 및 발현 세포주 개발을 추진하고 있다.

• Proceedings of the KSME Conference
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• 2005.11a
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• pp.70.1-70.1
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• 2005

• The Korean Journal of Pharmacology
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• v.26 no.1
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• pp.25-33
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• 1990

The responsiveness of various arterial smooth muscles isolated from rabbit to peptide YY (PYY) and the calcium source responsible for the muscles to contract were studied in vitro. PYY contracted the muscle strips of femoral, basilar and common iliac arteries more sensitively than renal, superior mesenteric and common carotid arteries. Common carotid and renal arteries were less sensitive to PYY $(p{\leqslant}0.05)$ than to NE; and basilar artery was more sensitive to PYY$(p{\leqslant}0.01)$ than to NE. A calcium channel blocker, verapamil and an inhibitor of intracellular calcium release, 3, 4, 5-Trime-thoxybenzoic arid 8-(diethylamino)octyl ester [TMB-8] significantly $(p{\leqslant}0.001)$ suppressed the concentration-response of the strips from femoral artery to PYY. When both verapamil and TMB-8 existed in normal PSS, the concentration-response to PYY was inhibited almost completely; and a similar suppression was observed when the muscle was incubated in calcium-free, ethyleneglycol-bis-(beta-aminoethyl ether)N,N,N',N'-tetraacetic acid [EGTA] containing PSS. The results of these experiments suggest that increased PYY activity in circulation may result in the more sensitive increase in the intracranial vascular resistance and the cerebral arterial pressure than the increased sympathetic activity and that both intra- and extracellular calcium are to be utilized for the PYY-induced contraction on arterial smooth muscle.

• Journal of Life Science
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• v.21 no.1
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• pp.102-109
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• 2011

The genioglossus muscle plays an important role in maintaining upper airway patency during inspiration; if this muscle does not contract normally, breathing disorders occur due to closing of the upper airway. These occur because of disorders of synaptic input to the genioglossus motoneurons, however, little is known about it. In this study, the distribution of GABA-, glycine-, and glutamate-like immunoreactivity in axon terminals on dendrites of the rat genioglossus motoneurons, stained intracellularly with horseradish peroxidase (HRP), was examined by using postembedding immunogold histochemistry in serial ultrathin sections. The motoneurons were divided into four compartments: the soma, and primary (Pd), intermediate (Id), and distal dendrites (Dd). Quantitative analysis of 157, 188, 181, and 96 boutons synapsing on 3 soma, 14 Pd, 35 Id, and 28 Dd, respectively, was performed. 71.9% of the total number of studied boutons had immunoreactivity for at least one of the three amino acids. 32.8% of the total number of studied boutons were immunopositive for GABA and/or glycine and 39.1% for glutamate. Among the former, 14.2% showed glycine immunoreactivity only and 13.3% were immunoreactive to both glycine and GABA. The remainder (5.3%) showed immunoreactivity for GABA only. Most boutons immunoreactive to inhibitory amino acids contained a mixture of flattened, oval, and round synaptic vesicles. Most boutons immunoreactive to excitatory amino acids contained clear and spherical synaptic vesicles with a few dense-cored vesicles. When comparisons of the inhibitory and excitatory boutons were made between the soma and three dendritic segments, the proportion of the inhibitory to the excitatory boutons was high in the Dd (23.9% vs. 43.8%) but somewhat low in the soma (35.7% vs. 38.2%), Pd (34.6% vs. 37.8%) and Id (33.1% vs. 38.7%). The percentage of synaptic covering of the inhibitory synaptic boutons decreased in the order of soma, Pd, Id, and Dd, but this trend was not applicable to the excitatory boutons. The present study provides possible evidence that the spatial distribution patterns of inhibitory and excitatory synapses are different in the soma and dendritic tree of the rat genioglussus motoneurons.

• Proceedings of the KSME Conference
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• 2007.05b
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• pp.2947-2950
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• 2007

A 3D human ventricular model is proposed to simulate an integrative analysis of heart physiology and blood hemodynamics. This consists of the models of electrophysiology of human cells, electric wave propagation of tissue, heart solid mechanics, and 3D blood hemodynamics. The 3D geometry of human heart is discretized to a finite element mesh for the simulation of electric wave propagation and mechanics of heart. In cellular level, excitations by action potential are simulated using the existing human model. Then the contraction mechanics of a whole cell is incorporated to the excitation model. The excitation propagation to ventricular cells are transiently computed in the 3D cardiac tissue using a mono-domain method of electric wave propagation in cardiac tissue. Blood hemodynamics in heart is also considered and incorporated with muscle contraction. We use a PISO type finite element method to simulate the blood hemodynmaics in the human ventricular model.

• The Korean Journal of Pharmacology
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• v.13 no.2
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• pp.11-17
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• 1977

The effects of varing concentrations of extracellular potassium on the positive inotropic actions of Aconiti tuber butanol fraction and ouabain were studied on isolated left atrium of rat. The patterns of active tension increment, such as time to peak and total duration of tension development, was contrasted in Aconiti tuber butanol fraction to ouabain. Ouabain did not induce significant shortening in time to peak and total duration of tension development, but Aconiti tuber produce significant shortening. The isometric tension and peak dF/dt were not significantly different at the range of extracellular potassium concentration $2mEq{\sim}10mEq$ per. liter in control studies. The ouabain-induced increase in active tension and peak dF/dt at 2mEq. per. liter potassium concentration was significantly different from that of 6mEq or 10mEq. per. liter, but there was no difference between 6mEq and 10mEq. per. liter. but Aconiti tuber is not. In contrast to ouabain, Aconiti tuber butanol fraction did not show potassium dependent positive inotropic effect. It produced almost same increment of tension and peak dF/dt at all the concentration of extracellular potassium concentrations in this experiment.

• Proceedings of the Korean Society of Food and Cookery Science Conference
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• 1987.06a
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• pp.92-106
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• 1987

$Na^{+}$는 체내에서 세포외액 (extracellular fluid)의 주요 양이온으로 세포내액과 세포외액은 세포막을 사이에 두고 $Na^{+}$와 $K^{+}$의 높은 농도의 차이를 유지하고 있다. 이러한 농도차이는 세포막에 있는 $Na^{+}$-K$^{+}$ATP ase의 활동에 의하여 유지되며 $Na^{+}$는 체액의 osmolarity와 혈장의 부피 유지, 신경흥분, 근육수축 및 영양소등의 이동에도 중요한 역할을 한다. 체내의 Na balance는 renin-aldosterone system에 의하여 신장에서의 배설조절로 이루어지며, 최근 Na대사에 관여하는 natriuretic hormone이 발견되고 있다. Na의 과잉섭취는 역학적 연구와 동물실험에서 고혈압의 유발인자로 제시되고 있으나, 임상적 연구에서는 Na제한이 혈압강하효과가 있다는 보고와 없다는 보고가 있어 결과가 뚜렷하지 않다. 이는 고혈압 환자중에는 salt-sensitive한 group자 salt-resistant group이 있다는 것과 산업화된 사회들의 Na 섭취량이 이미 너무 높은 수준으로 Na섭취증가와 혈압상승간의 관계를 현재의 연구 방법들로는 찾아내기 어렵다는 ‘saturation effect’로 설명한다. 그러나 Na섭취를 1일 70~100mEq.(NaCl 4.0~5.8g)이하로 줄이면 고혈압 발생이 현저히 감소하고 Na 섭취량이 1일 30mEq.(NaCl 1.7g)이하이면 고혈압은 거의 발생하지 않는다. 그러나 Na섭취가 1일 400mEq.(NaCl 23.2g)이상이 되더라도 인구 중 50~80%는 고혈압에 걸리지 않아 고혈압의 발생은 유전적 인자, 신장 기능의 부족에 의해 지배되고, Na이외에도 K, Ca등의 식이 인자 및 stress, 운동등의 환경적 요인들이 영향을 미친다. Na 섭취량은 자연식품에 들어있는 양 뿐 아니라, 가공과정, 조리가정, 식사 중에 첨가되는 양에 의하여 좌우되므로, Na 섭취량을 측정하기 매우 어렵다. 가장 널리 사용되는 방법은 24시간 소변 중 배설되는 Na의 양으로부터 추정하는 방법으로 우리나라의 경우, 이러한 방법으로 섭취량을 환산할 경우 1일 200~260mEq. (NaCl 11.6~15.1g) 정도이며 이중 80% 이상이 discretionary intake인 것으로 추정된다. 따라서 앞으로 Na섭취를 줄이도록 많은 노력을 기울여야 하겠다.

• The Korean Journal of Pharmacology
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• v.14 no.1_2
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• pp.1-11
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• 1978

The $Na^+$-and $K^+$-induced $Ca^{++}$ release was measured isotopically by Milipore filter technique in mitochondria isolated from rabbit ventricles. The release of $Ca^{++}$ from mitochondria could be induced by 1-3 mM of $Na^+$ added in incubating medium under the presence of 0.5mM EGTA to prevent the released $Ca^{++}$ from rebinding with mitochondrial membrane. The amount of $Ca^{++}$ released was increased by increasing the concentration of $Na^+$ added. 100mM $K^+$, in itself, did not induce the $Ca^{++}$ release from cardiac mitochondria, the $Na^+$-induced $Ca^{++}$ release, however, was potentiated by the presence of $K^+$. The potentiation of $Na^+$-induced $Ca^{++}$ release by $K^+$ was proportional to the $Na^+/K^+$ ratio presented in the incubating medium. Among the monovalent cations other than $Na^+$, the release of $Ca^{++}$ from cardiac mitochondria was shared only by $Li^+$. The $Na^+$-induced $Ca^{++}$ release could be also observed in the mitochondria isolated from liver and kidney. However, the $Na^+$ sensitivity was somewhat lower in liver and kidney mitochondria than in heart mitochondria. The release of $Ca^{++}$ induced by $Na^+$ in the mitochondria isolated from the experimentally produced failured heart was not different from that in the normal heart mitochondria, and was not directly modified by $10^{-6}{\sim}10^{-5}$ M of Ouabain. From the experiments, it was suggested that the $Ca^{++}$ released from mitochondria by $Na^+$ could be used in excitation-contraction coupling process to initiate the contraction of the cardiac myofibrils. Futhermore, it appeared that the phenomenon of $Ca^{++}$ release from cardiac mitochondria by $Na^+$ and $K^+$ might be related to the inotropic effect of digitalis glycoside which could bring about the increase of $Na^+$ or the reduction of $K^+$ intracellulary through the inhibition of $Na^+$, $K^+$-ATPase.