• The Korean Journal of Physiology
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• v.30 no.2
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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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• v.15 no.2
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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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• v.1 no.4
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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.

• Journal of the Korean Society of Food Science and Nutrition
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• v.21 no.5
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• pp.496-501
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• 1992

The present work tested the inhibitory effects of bile acids on the cholesterol biosynthesis and the activity of HMG-CoA reductase in cultured rat hepatocytes. The uptake of bile acids in hepatocytes were increased in according to the different bile acid concentrations and culture times. The rate of cholesterol synthesis in cells were inversely decreased to the bile acid concentrations and culture times. As expected, insulin injection (4 units/100g body weight) showed an enhancing effect of the cholesterol synthesis and the HMG-CoA reductase activity. The addition of bile acids in medium of insulin-treated hepatocytes also showed the suppressing effect. This effect was directly confirmed in isolated hepatic icrosomes by the test of HMG-CoA reductase activity. In the test of $Na^+$,$K^+$-ATPase activity in the isolated hepatocyte membrane, only the cholic acid did not stimulate the enzyme system. The reason of such difference is not obvious, but this result indicates that the cholic acid could be absorbed by simple diffusion.

• The Korean Journal of Physiology
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• v.21 no.2
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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.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1994.04a
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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.

• YAKHAK HOEJI
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• v.36 no.2
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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.

• Journal of Physiology & Pathology in Korean Medicine
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• v.17 no.2
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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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• v.22 no.2
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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.

• Korean Journal of Environmental Agriculture
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• v.20 no.1
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• pp.28-33
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• 2001

Lettuces were grown hydroponically in three different nutrient solutions, normal and 30 or 50 mM $KNO_3-added$ nutrient solutions, and the electrical conductivities of the nutrient solutions were 1.0, 4.5, and 6.5 dS/m, respectively. Lettuces grown in the $KNO_3-added$ nutrient solutions showed a decrease in the germination ratio and the lower indices of growth, such as plant height, stem diameter, leaf length, and leaf width. Microsomes were prepared from the roots of lettuce and characteristics of microsomal ATPases were investigated. The activities of microsomal ATPases grown in the 30 mM and 50 mM $KNO_3-added$ nutrient solutions were higher than that grown in the normal nutrient solution. The highest activities of microsomal ATPases were observed at pH 7.0 in all culture conditions. The activities of microsomal ATPases were increased in a reaction buffer solution containing high concentration of $K^+$, whereas they were decreased in a reaction buffer containing $Na^+$. The stimulating effect of $K^+$ in the reaction buffer was greater on the microsomal ATPases of lettuces grown in the $KNO_3-added$ nutrient solutions than that grown in the normal nutrient solution. These results imply that the activities of microsomal ATPases in the root tissue are increased as increasing the $KNO_3$ concentration in the hydroponical nutrient solution.