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Effects of Cyclobuxine D on Drug-Induced Contractions of the Isolated Rat Uterine Muscle and Potassium-Activated Calcium Channels in an Intestinal Smooth Muscle (흰쥐 적출 자궁의 수축 작용과 흰쥐 장관에 있어 칼륨에 의해 활성화되는 칼슘 채널에 대한 Cyclobuxine D의 영향)

  • Kwon, Jun-Tack;Lee, Jong-Hwoa;Park, Young-Hyun;Cho, Byung-Heon;Choi, Kyu-Hong;Kim, Yu-Jae;Kim, Jong-Bae;Kim, Chung-Mok;Kim, Chun-Sook;Cha, Young-Deog;Kim, Young-Suk
    • The Korean Journal of Pharmacology
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    • v.24 no.1
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    • pp.103-109
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    • 1988
  • Cyclobuxine D, extracted from Buxus microphylla var. koreana Nakai, is a steroidal alkaloid. Many pharmacological effects of cyclobuxine D were examined in our Lab. Cyclobuxine D showed a significant bradycardic effect in the rat heart and an inhibitory action on acetylcholine and $Ba^{++}-induced$ contraction of the longitudinal muscle isolated from the rabbit jejunum. In this study, we investigated the effect of cyclobuxine D on the contractile response-elicited by acetylcholine, oxytocin and $Ba^{++}$ in rat uterine. In order to analyse the inhibitory action of cyclobuxine D on the smooth muscle, we examined the inhibitory action of cyclobuxine D against the contractile response of the high potassium-depolarized rat ileum to calcium. Concentration-dependent decrease in the peak tension and duration of the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus was observed when cyclobuxine D was added to the organ bath. The isolated longitudinal muscle from the rat ileum was immersed calcium-depleted potassium-depolarizing solution. Ten minutes after, 1.8 mM $CaCl_2$ was added to muscle bath and elicited a biphasic increase in muscle tension. Cyclobuxine D $(6.2{\times}10^{-5}\;M)$ produced an appreciable inhibition of both components of the mechanical response. In addition, $3.1{\times}10^{-4}\;M$ cyclobuxine D, introduced at a point when the tonic response had reached its maximum level, caused the muscle to exhibit a rapid lose of tension. Based on these experimental results, we propose the possibility that the inhibitory action of cyclobuxine D on the acetylcholine, oxytocin and $Ba^{++}-induced$ contraction in the isolated rat uterus may be due to blocking potassium-activated calcium channels, voltage-sensitive calcium channels.

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Effect of $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the Spontaneous Contractions and Electrical Activities of Guinea-pig Stomach (기니피그 위 평활근의 자발적 수축과 전기적 활동에 대한 $Ca^{2+}$$Ca^{2+}$-길항제 영향)

  • Rhie, Sang-Ho;Kim, Ki-Whan
    • The Korean Journal of Physiology
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    • v.21 no.2
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    • pp.241-257
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    • 1987
  • The effects of external $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the spontaneous contractions and electrical activities were investigated in guinea-pig stomach in order to clarify the mechanism for the generation of slow waves. Electrical responses of circular smooth muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCl. All experiments were performed in tris-buffered Tyrode solution which was aerated with 100% $O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) The amplitude of spontaneous contractions was maximal at around 2-4 mM $Ca^{2+}$, whereas their frequency was inversely related with external $Ca^{2+}$ within the range of 0.5 to 16 mM $Ca^{2+}$. 2) Verapamil suppressed the amplitude of spontaneous contraction in a dose-dependent manner, while the frequency of spontaneous contractions was almost not changed over the whole concentration of verapamil $(0.01{\sim}5\;mg/l)$. 3) Manganese increased both the amplitude and the frequency of spontaneous contractions dose-dependently in low $Mn^{2+}$ (below 0.05 mM $Mn^{2+}$), while their amplitude and frequency were decreased in high $Mn^{2+}$ (above 0.1 mM $Mn^{2+}$). 4) The ampltude and maximum rate of rise of slow waves were incrased in high $Ca^{2+}$ solution. In $Ca^{2+}-free$ solution, the spontaneous contractions recorded simultaneously with slow waves ceased and tonic contraction ($Ca^{2+}-free$ contracture) was developed in parallel with membrane depolarization and the disappearance of slow waves. 5) Verapamil (1 mg/1) decreased the amplitude and maximum rate of rise of slow waves and it depolarized the membrane by about 6 mV, whereas the frequency of slow waves was not affected by verapamil. 6) Manganese showed different characteristic effects between low and high $Mn^{2+}$ on the slow waves: In low $Mn^{2+}$ (0.05 mM $Mn^{2+}$), the initial rapid increases and the subsequent gradual decreases in three parameters of slow waves (amplitude, rate of rise, and frequency of slow waves) till a new steady state were observed. However, in high $Mn^{2+}$ (0.5 mM $Mn^{2+}$) slow waves disappeared and membrane was depolarized. From the above results, the following conclusions could be made: 1) $Ca^{2+}$ is necessary for a generation of the slow waves, even though it is small amount. 2) Verapamil suppresses the spontaneous contractions of gastric antral strip by the decreases in amplitude and maximum rate of rise of slow waves, while this drug does not block the $Ca^{2+}-channel$ involved in the generation of slow waves. 3) Manganese has dual actions on the $Ca^{2+}-channels$; the $Ca^{2+}-channel$ involved in the generation of slow waves (or Na-Ca exchange system) or the channel for the generation of spike potentials are stimulated by a low concentration of $Mn^{2+}$, while both the $Ca^{2+}$. Channels are blocked by high concentration of $Mn^{2+}$.

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Relation of Ethanol and Calcium to Contractile and Electrical Activity of Cat Stomach (고양이 위(胃)의 수축 및 전기활동에 대한 에탄올과 칼슘의 관계)

  • Kim, Myung-Suk;Sim, Sang-Soo;Yoon, Shin-Hee;Han, Sang-Jun;Kim, Chung-Chin;Choi, Hyun
    • The Korean Journal of Physiology
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    • v.21 no.2
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    • pp.259-272
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    • 1987
  • This was study carried out to investigate the effect of calcium on spontaneous contraction and electrical activity induced by ethanol in gastric smooth muscle. After peeling off the mucous membrane from the isolated whole stomach of 102 cats, two kinds of small muscle preparations $(2.0{\times}0.2\;cm)$, one longitudinal and the other circular, were excised from the fundus, the corpus and the antrum portion of each whole stomach specimen. The isometric contraction of the small muscle preparation was measured in a cylinder-shaped chamber filled with Krebs-Ringer-dextrose solution (pH 7.4, temperature $36{\pm}0.5^{\circ}C$) bubbling with 5% $CO_2$ in $O_2$. A large muscle preparation $(5.0{\times}1.2\;cm)$ was excised from the anterior wall of the corpus-antrum portion of the same specimen in 72 of 102 cats. The gastric electrical activity (slow wave and spike potential) was monopolarly recorded by four capillary electrodes (Ag-AgCl), of which two were placed on the corpus and two on the antrum, in a muscle chamber filled with the same solution as described above. Changes in the amplitude of the contraction, frequency of the gastric slow wave and the production of the spike potential were observed after adding ethanol and/or under the treatments with verapamil, $CaCl_2$ and Ca-free Krebs-Ringer-dextrose solution. The results were as follows: 1) After adding ethanol, the spontaneous phasic contraction of the corpus was reduced dose-dependently (0.125-2.0%), which was totally abolished by higher concentrations (2.0-8.0%) of ethanol. 2) The corporal phasic contraction was also completely abolished by verapamil $(3{\times}10^{-5}\;M)$ or Ca-free Krebs-Ringer-dextrose solution. The contraction was increased by $CaCl_2\;(1.8{\times}10^{-3}\;M)$, but the inhibitory effect of ethanol on the contraction persisted even under the treatment with $CaCl_2$. 3) At higher concentrations, ethanol caused tonic contraction of both preparations from the fundus, the corpus and the antrum in a dose-dependent manner. The tonic contraction of the fundus produced by ethanol was not influenced by $CaCl_2$ or verapamil, whereas the tonic contraction was not produced by ethanol in tile Ca-free solution. 4) Frequency of gastric slow wave was decreased dose-dependently by the addition of ethanol (0.25-1.0%), and tile slow wave was not produced by higher concentration of ethanol (2.0%). 5) The frequency of slow wave was significantly reduced by verapamil only and the inhibitory influence of ethanol on the slow wave frequency was reinforced by verapamil. 6) The treatment of $CaCl_2$ increased significantly the slow wave frequency, and attenuated the inhibitory effect of ethanol on the frequency. It is therefore suggested that ethanol regulates the phasic contraction and the production of slow wave by interfering with the transport of calcium in the stomach muscle of the cat.

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The Effect of Firm Characteristics on the Relationship between Managerial Ability and Firm Performance (기업특성이 경영자능력과 경영성과의 관계에 미치는 영향)

  • Cho, Sang-Min;Yoo, Ji-Yeon
    • Management & Information Systems Review
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    • v.37 no.1
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    • pp.103-122
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    • 2018
  • This paper expands the results of previous studies indicating that manager's ability positively affects business performance to analyze whether the degree to which the role of manager's ability improves business performance appears differently according to the characteristics of enterprises. As for the characteristics of enterprises, whether enterprises correspond to enterprises with high levels of funding constraints or late movers in the market is considered. Enterprises with high levels of funding constraints greatly require managers' roles not only for efficient use of funds but also for smooth financing. Late movers require more judgments of professional managers to overcome insufficient resources held and low profitability. In the case of enterprises with corporate characteristics with high dependency on the manager, the business performance is expected to greatly vary with the ability of the manager. The empirical analysis was conducted with listed companies from 2010 to 2014, manager's ability was measured by first measuring the efficiency of the entire enterprise through data envelopment analysis (DEA) using the methodology of Demerjian et al.(2012) and removing enterprise characteristics factors thereafter. Business performance was measured by the return on industrial fixed assets. The results of the empirical analysis indicated that the degree to which manager's ability improves business performance was higher in managerial competence enhances managerial performance in enterprises with high levels of funding constraints and late movers. Business performance is considered to have been improved further in cases where manager's ability is high because investments were made more efficiently through smooth funding. In addition, in the case of late movers in relatively poor environments, business performance was improved further because high manager's ability induced efficient decision making. In this paper, we extend the precedent study that the manager's ability improves the management performance, and confirm that the manager's ability to improve the managerial performance can be different according to the situation of the company. In addition, it is meaningful to analyze empirically whether a company's managerial ability is more important. This paper expanded the results of previous studies indicating that manager's ability improves performance to identify that the degree to which manager's ability improves business performance may appear differently according to situations in which enterprises are placed. In addition, this paper is meaningful in that it empirically analyzed what enterprises require manager's ability more importantly.

Caries Prevention Effect of Water Fluoridation in Gimhae, Korea (김해시 수돗물불소농도조정사업의 영구치 우식예방효과)

  • Kim, Han-Na;Cho, Hyun-Hee;Kim, Min-Ji;Jun, Eun-Joo;Han, Dong-Hun;Jeong, Seung-Hwa;Kim, Jin-Bom
    • Journal of dental hygiene science
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    • v.14 no.4
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    • pp.448-454
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    • 2014
  • The aim of this study was to evaluate the effect of a water fluoridation program (WFP) on prevention of dental caries in Gimhae City, Korea, with reference to the results of 2012 Korean National Oral Health Survey (KNOHS). In WFP population, 972 subjects including 8-, 10- and 12-year-old children in Gimhae City were examined in 2009. The WFP in Gimhae city has been implemented since 1999. 1872 subjects in non-fluoridated small and medium sized cities similar to Gimhae city were selected from 2012 KNOHS data as the control population. Two dentists who received training in KNOHS with an inter-examiner-agreement examined oral health status of all subjects. To assess the effects of WFP on dental caries, caries preventive fraction was estimated by assessing the differences of decayed, missing, and filled teeth (DMFT) index and decayed, missing, and filled surfaces (DMFS) index, DMFS in pit and fissures and smooth surfaces between WFP population and the control. Univariate analysis of variance adjusted for gender and number of fissure-sealed teeth or surfaces was conducted. DMFT of 12-year-old subjects (n=354) in WFP and control population (n=1,518) were 1.60 and 2.12, respectively, with an estimated prevention effect of 24.7%. Caries preventive fraction on pit and fissure, and smooth surfaces of WFP subjects was estimated 27.5% and 24.0%, among subjects aged 12 years, respectively. WFP in Gimhae City, Korea reduced the prevalence of dental caries and is recommended as a public oral health program where a fluoride-containing toothpastes are commonly used.

Study on the Clonality of Endothelial Cell Proliferation in Plexiform Lesions in Patients with Pulmonary Hypertension Associated with CREST Syndrome (CREST 증후군에 동반된 폐고혈압 환자에서 총상병변내 내피세포 증식의 클론성에 관한 연구)

  • Lee, Sang-Do;Jeon, Yong-Gam;Lee, Ji-Hyun;Shim, Tae-Sun;Lim, Chae-Man;Koh, Yun-Suck;Kim, Woo-Sung;Kim, Dong-Soon;Kim, Won-Dong;Tuder, Rubin M.
    • Tuberculosis and Respiratory Diseases
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    • v.47 no.2
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    • pp.150-160
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    • 1999
  • Background: The CREST syndrome is an indolent form of progressive systemic sclerosis. Although its clinical progress is indolent, pulmonary hypertension(PH) associated with CREST syndrome have grave prognosis with over 40 percent mortality rate at 2 year follow-up. But the pathogenesis of pulmonary hypertension in this disease is not known, and classified as either primary or secondary PH. Clonality of endothelial cell proliferation in plexiform lesion is a molecular marker which allows distinction between primary and secondary PH. We performed this study to know whether the PH associated with CREST syndrome is a variant of primary PH or is a secondary PH. Methods: We assessed the X-chromosome inactivation based on the methylation pattern of the human androgen-receptor gene by PCR(HUMARA). Endothelial cells in plexiform lesions from female patients(n=3) with PH associated with CREST syndrome were microdissected from paraffin blocks. Vascular smooth muscle cells and lung parenchyma were also microdissected for clonality studies. Results: The proliferating endothelial cells in 14 plexiform lesions were all polyclonal. Similarly proliferated smooth muscle cells from 5 vessels with medial hypertrophy were also polyclonal. Conclusion: These results suggest that the pulmonary hypertension associated with CREST syndrome has different pathogenesis from primary PH and to be classified as secondary PH.

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Relationship between Pleural Adenosine Deaminase Level and Patterns of Pleural Enhancement in Patients with a Tuberculous Pleural Effusion on CT Scan (결핵성흉막염 환자에서 흉수 내 아데노신 탈아민효소(Adenosine deaminase)의 활성도와 CT에서 흉막의 조영증강 양상과의 연관성)

  • Lee, Hwa Yeun
    • Tuberculosis and Respiratory Diseases
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    • v.62 no.6
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    • pp.486-491
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    • 2007
  • Background: This study examined the relationship between the pleural adenosine deaminase (ADA) level and the patterns of pleural enhancement in patients with a tuberculous pleural effusion (TPE) shown on a CT scan. Methods: The charts and CT findings of 44 patients with TPE from February 2002 to October 2006 were reviesed retrospectively. A diagnosis of TPE was made by the pleural ADA level with a follow-up (24/44), sputum smear or culture of sputum (16/44), pleural fluid culture (3/44) or pleural biopsy (1/44). The patients were divided into two groups according to the ADA level(Group I [n=12]: 40-70, Group II [n=32]: >70 U/L). The presence or absence, maximal thickness and patterns of pleural enhancement were analyzed. The pattern of pleural enhancement was classified into diffuse or focal, smooth or irregular and interrupted or continuous. The difference in CT findings between groups I and group II were analyzed using an unpaired T test, Chi-square test and Z test. Results: All 44 patients showed diffuse pleural enhancement on the CT scans. The maximal pleural thickness of groups I and II was $1.83{\pm}1.03mm$ (1-4 mm) and $3.63{\pm}1.78mm$ (1-8 mm), respectively (p =0.0002). Pleural thickening ${\geq}5mm$ was only demonstrated in 31.3% of patients in group II (10/32). Diffuse interrupted pleural thickening was noted in 91.7% (11/12) of patients in group I and 62.5% (20/32) in group II, respectively. Diffuse continuous pleural thickening was observed in 8.3% (1/12) of patients in group I and 37.5% (12/32) in group II, respectively (p=0.0748). Conclusion: Pleural thickening ${\geq}5mm$ on the contrast enhanced CT is rare in patients with lymphocyte-dominant TPE in whom the pleural ADA level is between 40-70 U/L.

Identification of Matrix Mineralization-Related Genes in Human Periodontal Ligament Cells Using cDNA Microarray (cDNA microarray에 의한 치주인대세포의 광물화 결절형성에 관여하는 유전자들의 분석)

  • Shin, Jae-Hee;Park, Jin-Woo;Yeo, Shin-Il;Noh, Woo-Chang;Kim, Moon-Kyu;Kim, Jung-Chul;Suh, Jo-Young
    • Journal of Periodontal and Implant Science
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    • v.37 no.sup2
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    • pp.447-463
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    • 2007
  • Periodontal ligament (PDL) cells have been known as multipotential cells, and as playing an important rolesin periodontal regeneration. The PDL cells are composed of heterogeneous cell populations which have the capacity to differentiate into either cementoblasts or osteoblasts, depending on needs and conditions. Therefore, PDL cells have the capacity to produce mineralized nodules in vitro in mineralization medium which include ascorbic acid, ${\beta}$-glycerophosphate and dexamethasone. In spite of these well-known osteoblast like properties of PDL cells, very little is known about the molecules involved in the formation of the mineralized nodules in the PDL cells. In the present study, we analysed gene-expression profiles during the mineralization process of cultured PDL cells by means of a cDNA microarray consisting of 3063 genes. Nodules of mineralized matrix were strongly stained with alizarin red S on the PDL cells cultured in the media with mineralization supplements. Among 3,063 genes analyzed, 35 were up-regulated more than two-fold at one or more time points in cells that developed matrix mineralization nodules, and 38 were down-regulated to less than half their normal level of expression. In accord with the morphological change we observed, several genes related to calcium-related or mineral metabolism were induced in PDL cells during osteogenesis, such as IGF-II and IGFBP-2. Proteogycan 1, fibulin-5, keratin 5, ,${\beta}$-actin, ${\alpha}$-smooth muscle actin and capping protein, and cytoskeleton and extracellular matrix proteins were up-regulated during mineralization. Several genes encoding proteins related to apoptosis weredifferentially expressed in PDL cells cultured in the medium containing mineralization supplements. Dkk-I and Nip3, which are apoptosis-inducing agents, were up-regulated, and Btf and TAXlBP1, which have an anti-apoptosis activity, were down-regulated during mineralization. Also periostin and S100 calciumbinding protein A4 were down-regulated during mineralization.

GS354 and GS389: New Type of Calcium Channel Blockers (GS354, GS389: 새로운 칼슘 길항제)

  • Chang, Ki-Churl;Sohn, Dong-Ryul;Chong, Won-Seog;Chung, Soo-Youn;Lee, Young-Soo;Kim, Si-Hwan;Noh, Hong-Kee;Suh, Joung-Seo;Takizawa, Satoko;Karaki, Hideaki
    • The Korean Journal of Pharmacology
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    • v.27 no.1
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    • pp.45-52
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    • 1991
  • The inhibitory effects of GS354 and GS389 on cytosolic $Ca^{2+}$ level ($[Ca^{2+}]_{1}$; measured with fura-2 fluorescence) and muscle tension in vascular smooth muscle of rat thoracic aorta were investigated. Both GS354 and GS389 inhibited the contractions induced by high $K^+$ or by norepinephrine. The vasodilator effect of GS354 was accompanied by a decrease in $[Ca^{2+}]_{1}$. The inhibitory effect on high $K^+-stimulated$ $[Ca^{2+}]_{1}$ was antagonized by a $Ca^{2+}$ channel activator, Bay K8644. However, the inhibitory effect on muscle tension was not antagonized by Bay K8644. These results suggest that GS354 inhibits $Ca^{2+}$ channels to decrease $[Ca^{2+}]_{1}$ and also decreases $Ca^{2+}$ sensitivity of contractile elements. The inhibitory effects of GS389 was accompanied by the increase in tissue fluorescence. This increment was not due to fura-2 fluorescence but to endogeneous pyridine nucleotides, suggesting that GS389 has an effect to inhibit mitochondrial function. Because of this interference, effects of GS389 on $[Ca^{2+}]_{1}$ was obscured. However, since sequential addition of Bay K8644 in the presence of GS389 further increased the fluorescence but not muscle tension, this compound seems to have the effects to inhibit $Ca^{2+}$ channels and to decrease $Ca^{2+}$ sensitivity of contractile elements.

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Quantitative Measurement of Membrane $Na^+-K^+$ ATPase Activity using Thallium-201 : Comparison with Rubidium-86 (Thallium-201을 이용한 세포막 $Na^+-K^+$ ATPase 활성도 측정: Rubidium-86 측정법과의 비교)

  • Lee, Jae-Tae;Lee, In-Kyu;Sohn, Sang-Kyun;Lee, Kyu-Bo
    • The Korean Journal of Nuclear Medicine
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    • v.32 no.2
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    • pp.121-128
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    • 1998
  • Purpose: $Na^+-K^+$ ATPase activity has been estimated by the degree of inhibition of cation transport by cardiac glycosides (ouabain) using Rb-86 as a substrate. The biological characteristisc of T1-201 is known to be similar to those of potassium as a transport substrate in the presence of glucose, insulin or phobol myristate acetate (PMA). The purpose of this study was to measure ouabain sensitive $Na^+-K^+$ ATPase activity using T1-201 and compare with that using Rb-86. Materials and Methods: Smooth muscle cells isolated from rat aorta or human placental umbilical artery were cultured, and used to measure cellular $Na^+-K^+$ ATPase activity. $Na^+-K^+$ ATPase activity was measured as a percentage decrease in cellular uptake of T1-201 or Rb-86 by ouabain under the presence of glucose, insulin or PMA in media. Results: $Na^+-K^+$ ATPase activity measured with T1-201, as a transport substrate, was not different from those measured with Rb-86 in rat or human smooth muscle cell preparation. Incubation with high concentration glucose resulted in about 30% decrease in enzyme activity. In contrast, insulin or PMA resulted in 10-70% or 28% increases from baseline activity, respectively. Conclusion: These results suggests that 71-201 could replace Rb-86 in measurement of ouabain sensitive $Na^+-K^+$ ATPase activity in vitro. High level of glucose concentration decreased cellular $Na^+-K^+$ ATPase activity, but insulin or PMA increased it.

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