• The Korean Journal of Physiology
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• 제30권2호
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• pp.257-267
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• 1996

Diabetes mellitus is associated with a wide range of pathophysiologic changes in the kidney. This study was designed to examine the mechanisms by which glucose modulates the expression of polarized membrane transport functions in primary cultured rabbit renal proximal tubule cells. Results are as follows: The rate of 30 minute $Rb^{+}$ uptake was significantly higher($137.76{\pm}5.40%$) in primary renal tubular cell cultures treated with 20 mM glucose than that of 5 mM glucose. Not the level of mRNA for the ${\alpha}$ subunit of Na, K-ATPase but that of ${\beta}$ subunit was elevated in primary cultures treated with high glucose. The initial rate of methyl-${\alpha}$-D-glucopyranoside(${\alpha}$-MG) uptake was significantly lower($71.91{\pm}3.02%$) in monolayers treated with 20 mM glucose than that of 5 mM glucose. There was a tendency of an increase in phlorizin binding site in cells treated with 5 mM glucose. However, 3-O-methyl-D-glucose(3-O-MG) uptake was not affected by glucose concentration in culture media. TPA inhibited $Rb^{+}$ uptake by $63.61{\pm}1.94\;and\;45.80{\pm}1.36%$ and ${\alpha}$-MG uptake by $48.54{\pm}3.69\;and\;41.87{\pm}6.70%$ in the cells treated with 5 and 20 mM glucose, respectively. Also TPA inhibited mRNA expression of Na/glucose cotransporter in cells grown in 5mM glucose medium. cAMP significantly stimulated ${\alpha}$-MG uptake by $114.65{\pm}5.70%$ in cells treated with 5mM glucose, while it did not affect ${\alpha}$-MG uptake in cell treated with 20 mM glucose. However, cAMP inhibited $Rb^{+}$ uptake by $76.69{\pm}4.16\;and\;66.87{\pm}2.41%$ in cells treated with 5 and 20 mM glucose, respectively. In conclusion, the activity of the renal proximal tubular Na,K-ATPase is elevated in high glucose concentration. In contrast, the activity of the Na/glucose cotransport system is inhibited. High glucose may in part affect the activity of the Na,K-ATPase and the Na/glucose cotransport system by controlling the protein kinase C and/or A signal transduction pathway in primary cultured renal proximal tubule cells.

• Journal of Radiation Protection and Research
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• 제15권2호
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• pp.1-6
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• 1990

An attempt was made to test the possibility of a major role for the $Na^{+}-K^{+}$ adenosine triphosphatase (ATPase)system in the diuresis induced by uranyl nitrate(UN). Fisher 344 rats were intravenously injected with UN(5 mg/kg, 15 mg/kg and 30 mg/kg). Urinary excretion of $Na^{+}\;and\;K^{+}$ significantly increased in 24 h exposure on the UN and then decreased below the normal level 3 days after the treatment. $Na^{+}-K^{+}$ ATPase activity of kidney was significantly inhibited in high dosages of UN 15mg/kg and UN 30 mg/kg 3-5 days after injection. And then the recovery of the enzyme activity was observed within 5-10 days after injection, at which the regeneration of the tubular cells occurred.

• The Korean Journal of Physiology and Pharmacology
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• 제1권4호
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• pp.367-376
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• 1997

The effect of an organic peroxide, t-butylhydroperoxide (t-BHP), on glutamate uptake was studied in synaptosomes prepared from cerebral cortex. t-BHP inhibited the $Na^+-dependent$ glutamate uptake with no change in the $Na^+-independent$ uptake. This effect of t-BHP was not altered by addition of $Ca^{2+}$ channel blockers (verapamil, diltiazem and nifedipine) or $PLA_2$ inhibitors (dibucaine, butacaine and quinacrine). However, the effect was prevented by iron chelators (deferoxamine and phenanthroline) and phenolic antioxidants (N,N'-diphenyl-phenylenediamine, butylated hydroxyanisole, and butylated hydroxytoluene). At low concentrations (＜1.0 mM), t-BHP inhibited glutamate uptake without altering lipid peroxidation. Moreover, a large increase in lipid peroxidation by $ascorbate/Fe^{2+}$ was not accompanied by an inhibition of glutamate uptake. The impairment of glutamate uptake by t-BHP was not intimately related to the change in $Na^+-K+-ATPase$ activity. These results suggest that inhibition of glutamate uptake by t-BHP is not totally mediated by peroxidation of membrane lipid, but is associated with direct interactions of glutamate transport proteins with t-BHP metabolites. The $Ca^{2+}$ influx through $Ca^{2+}$ channel or $PLA_2$ activation may not be involved in the t-BHP inhibition of glutamate transport.

• 한국식품영양과학회지
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• 제21권5호
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• pp.496-501
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• 1992

간세포내 두가지 microsome효소인 HMG-CoA reductase와 cholesterol-$7{\alpha}$-hydroxylase는 콜레스테롤 합성과 담즙산으로의 분해의 조절효소임은 이미 알려진 사실이다. 본 실험에서는 콜레스테롤의 대사산물인 4종류 담즙산들이 간세포내의 콜레스테롤 합성 및 HMG-CoA reductase활성에 미치는 효과를 조사하였다. 간세포의 배양에서 간세포로의 담즙산 흡수는 배지내 농도(1mM~10mM)와 배양시간(1/2~3hr)의 차이에 따라 비례적으로 증가하였다. 콜레스테롤 합성저해에 대한 담즙산의 효과는 배지내 담즙산의 농도 및 배양시간에 따라 크게 감소하였다. 분리시킨 microsome내 HMG-CoA reductase의 활성에 대한 담즙산의 저해효과는 insulin 투여에 의하여 효소활성을 촉진시킨 경우에서도 뚜렷하였으며 콜레스테롤 합성 역시 저하되었다. 분리시킨 간세포막 내 $Na^+$,$K^+$-ATPase의 활성은 1.8~2.5mM정도의 배지내 담즙산 농도까지 증가함을 보였으나 cholic acid 흡수는 상기 효소의 활성에 거의 영향을 주지 않는 것으로 나타났다. 이러한 이유는 아직 불분명하나 1차 대사산물인 cholic acid의 흡수는 단순확산에 의한 것으로 사료되며 이에 대한 더 많은 연구가 요구된다.

• The Korean Journal of Physiology
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• 제21권2호
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• pp.157-167
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• 1987

Benzyl alcohol is known to have dual effect on the red blood cell shape change. At low concentration up to 50 mM benzyl alcohol transformed the shape from discocyte to stomatocyte by preferent binding to the inner hemileaflet, however, at higher concentratransformed the shape from discocyte to stomatocyte by preferential binding to the inner monolayer, however, at higher concentration above 50 mM benzyl alcohol transformed to echinocyte by affecting both monolayers. These results suggest that the effect of benzyl alcohol on the red blood cell shape and $Ca^{++}$ transport across cardiac cell membranes to assess the effects of the drug on the structures and functions of the biological cell membranes. The results are as follows: 1) Benzyl alcohol up to 40 mM caused progressive stomatocytic shap change of the red blood cell but above 50 mM benzyl alcohol caused echinocytic shape change. 2) Benzyl alcohol up to 40 mM inhibited both osmotic hemolysis and osmotic volume change of the red blood cell in hypotonic and hypertonic NaCl solutions, respectively. 3) Benzyl alcohol inhibited both Bowditch Staircase and Wood-worth Staircase phenomena at rat left auricle. 4) Benzyl alcohol at concentration of 5 mM increased $Ca^{++}-ATPase$ activity of red blood cell ghosts slightly but above S mM benzyl alcohol inhibited the $Ca^{++}-ATPase$ activity. 5) Benzyl alcohol at concentrations of 5 mM and 10 mM increased $Ca^{++}-ATPase$ activity slightly at rat gastrocnemius muscle S.R. but above 10 mM benzyl alcohol inhibited the $Ca^{++}-ATPase$ activity. Above results indicate that benzyl alcohol inhibit water permeability and $Ca^{++}$ transport across cell membranes in part via effects on the fluidity and transition temperatures of the bulk lipid by preferential intercalation into cytoplasmic monolayer and in part via other effect on the conformational change of active sites of the $Ca^{++}-ATPase$ molecule extended in cytoplasmic face.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1994년도 춘계학술대회 and 제3회 신약개발 연구발표회
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• pp.335-335
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• 1994

Possibility whether lead ingestion can cause selective toxicity to central serotonergic nervous system in rats was tested. Three groups of wistar rats; 1)Control, 2) Low dose and 3) High dose groups, were prepared. In prenatally lead-exposed rats, until parturition from dams, rat pups were intoxicated via placenta of mother rats having received drinking water containing either 0%(control ), 0.05%(low dose) or 0.2%(high dose) of lead acetate respectively, In postnatally lead-exposed rats, right after parturition from dams rat pups received drinking water containing either 0％ (control), 0.05%(low dose) or 0.2％(high dose) of lead acetate. At 2, 4, 6 and 8 weeks of age, tryptophan hydroxylase (TPH) activity and Na$\^$+//K$\^$+/-ATPase activity were measured in 4 areas of rat brain; Telencephalon, Diencephalon, Midbrain and Pons/Medulla. TPH activities were assayed by modified method of Beevers et al. (1983) using L-(5-$^3$H)-tryptophan as substrate. TPH activity was determined as a criterion of lead poisoning to central serotonergic nervous system and Na$\^$+//K$\^$+/-ATPase activity as a criterion of non specific lead poisoning to any kinds of tissues. Selective toxicity of lead poisoning to central serotonergic nervous system was evaluated by the changes of TPH activities without concomitant changes of Na$\^$+//K$\^$+/-ATPase activities. In prenatally lead-exposed rats. this selectivity was found in Telencephalon (2 weeks of age), Diencephalon/Midbrain (2 weeks of age), Midbrain (4 and 6 weeks of age), Pons/Medulla (2, 4 and 6 weeks of age) In rats exposed to low dose of lead and Pons/Medulla (2 weeks of age) to high dose of lead. In postnatal Iy lead-exposed rats, this selectivity was found in Telencephalon (8 weeks of age), Diencephalon(8 weeks of age), Pons/Medulla (6 and 8 weeks of age) in rats exposed to low dose of lead and Pons/Medulla (8 weeks of age) to high dose of lead. These results suggest that lead poisoning may exhibit selective toxicity to central serotonergic nervous system.

• 약학회지
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• 제36권2호
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• pp.129-136
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• 1992

The effects of ginseng saponins, gypsophila saponin, sodium dodecyl sulfate(SDS), and Triton X-100 on membrane $K^+-dependent$ phosphatase activity which is lipid dependent and represents dephosphorylation step of the complete Na+, $K^+-ATPase$ reaction were investigated in this study to elucidate whether the effects of ginseng saponins are due to the detergent action, using sarcolemma enriched preparation isolated from dog ventricle. $Na^+$, $K^+-ATPase$ and $K^+-dependent$ phosphatase activities of cardiac sarcolemma were about $143\;{\mu}mol$ Pi/mg protein/hr and $34\;{\mu}mol$ p-nitrophenol/mg protein/hr, respectively. While ginseng saponins (triol>total>diol) inhibited $K^+-dependent$ phosphatase activity, gypsophila saponin, and low dose of SDS($0.4\;{\mu}g/{\mu}g$ protein), and Triton X-100 ($0.6\;{\mu}g/{\mu}g$ protein) increased the enzyme activity, indicating disruptive effect of detergents on membrane barriers. The activating effect of low doses of Triton X-100 on membrane $K^+-dependent$ phosphatase appeared at concentration decreasing light scattering. However, the inhibitory effect of ginseng saponin appeared before a decrease in light scattering. These results suggest that low concentrations of ginseng saponins inhibit the membrane $K^+-dependent$ phosphatase by interacting directly with enzyme before membrane disruption.

• 동의생리병리학회지
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• 제17권2호
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• pp.542-548
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• 2003

The present study was aimed to investigate whether glycyrrhizin, which is the major component of Glycyrrhiza uralensis, has an antioxidant effect and regulatory effect on Na,K-ATPase in gentamicin-induced acute renal failure (ARF) rats . It is well known that reactive oxygen species (ROS), such as superoxide anion and hydroxyl radical, are main pathophysiological factor in gentamicin-induced ARF. Glycyrrhizin showed potent in vitro antioxidant activity, especially superoxide scavenging activity, in a dose-dependent manner. Plasma lipid peroxide level was restored to normal level by oral administration of glycyrrhizin (200 mg/kg) in the gentamicin-induced ARF rats. The expression of Na,K-ATPase α1 subunit was restored in the gentamicin-induced ARF rats by administration of glycyrrhizin, whereas β1 subunit was not restored. The renal functional parameters including urine volume, cleatinine clearance, urine osmolality, solute-free water reabroption were also partially restored in gentamicin-ARF rats by administration of glycyrrhizin. Taken together, the amelioration of renal functions and the expression of sodium pump by administration of glycyrrhizin in the gentamicin-induced ARF was appear to be mediated by the scavenging of ROS.

• Archives of Pharmacal Research
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• 제22권2호
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• pp.137-142
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• 1999

Anti-ulcer activity of newly synthesized acylquinoline derivatives was investigated. For the in vitro screening, the effects of compounds on gastric $H^{+}/K^{+}$ ATPase isolated from hog and rabbit were examined. Among them, AU-090, AU-091, AU-254, AU-413 and AU-466 exhibited good in vitro activity on both enzymes. To correlate the in vitro activity with in vivo action, the effects of the compounds on the basal gastric acid secretion were studied. Some derivatives showed considerable anti-secretory activities, and AU-413 was selected for further studies. AU-413 protected gastric damage induced by either ethanol or NaOH dose dependently when given orally. $ED_{50}$ values of 12 mg/kg, p.o. (ethanol) and 41 mg/kg, p.o. (NaOH) were obtained. In addition, histamine-stimulated gastric secretion was reduced upon AU-413 administration. Taken together, newly synthesized acylquinoline derivatives, especially AU-413, is worthy of further investigation to be developed as an anti-ulcer agent.

• 한국환경농학회지
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• 제20권1호
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• pp.28-33
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• 2001

본 시험에서 사용된 상추는 대조구인 양액과 양액에 30 mM $KNO_3$, 혹은 양액에 50 mM $KNO_3$를 첨가한 염류농도가 다른 3가지의 양액에서 재배하였으며 이들 양액의 EC는 각각 1.0, 4.5, 6.5 ds/m이었다. 상추의 생육은 처리간에 차이를 보였으며 $KNO_3$를 첨가하여 염류농도를 높여준 용액에서 재배한 상추는 잎끝이 마르는 생리적 장해를 보이면서 발아율의 감소는 물론 초장, 경태, 엽장 및 엽폭 등 성장이 대조구와 비교하여 현저히 부진하였다. 이들 양액에서 자란 상추의 뿌리로부터 마이크로솜을 분리하여 ATPase의 특성을 조사하였다. 마이크로솜 ATPase의 활성은 대조구에 비하여 양액에 30 mM $KNO_3$와 50 mM $KNO_3$를 첨가한 용액에서 자란 상추에서 더 높았다. 상추뿌리로부터 분리한 마이크로솜 ATPase의 총활성은 재배양액 조건에 관계없이 pH 7.0에서 최대로 나타났다. ATPase의 활성은 반응용액의 $K^+$ 농도를 증가시키면 증가하였고 반응용액에 $Na^+$ 농도를 증가시키면 감소하였다. $K^+$에 의한 활성증가 효과는 양액에서 재배한 대조구보다 $KNO_3$를 첨가하여 EC를 높여준 양액에서 재배한 상추뿌리의 마이크로솜 ATPase에서 더 크게 나타났다. 이러한 결과는 생육환경내 $KNO_3$ 농도의 증가에 따라 뿌리의 생리활성을 조절하는 ATPase의 활성이 증가함을 보여준다.