• The Korean Journal of Physiology
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• v.28 no.2
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• pp.159-167
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• 1994

The contraction of rabbit basilar artery was examined as a function of changes in the $Na^+$ electrochemical gradient in order to determine the contribution of $Na^+/Ca^{2+}$ exchange to the modulation of contractility. Ouabain $(10^{-5}\;M)$ or $K^+-free$ Tyrode solution caused an increase in tonic tension even in the presence of a $Ca^{2+}$ channel blocker $(10^{-6}\;M\;verapamil)$ and an ${\alpha}-receptor$ blocker $(10^{-5}\;M\;phentolamine)$. After treatment with ouabain $(10^{-5}\;M)$, contractions were augmented by reduction of external $Na^+$ concentration. The longer the treatment with ouabain $(10^{-5}\;M)$ was, the larger the amplitude of $Na^+-free$ contracture was. $Na^+-free$ contracture wag induced by either substitution of equimolar Tris for $Na^+$ or substitution of equimolar $Li^+\;for\;Na^+$. The competition between $Na^+\;and\;Ca^{2+}$ for the $Na^+/Ca^{2+}$ exchange carrier would exist, because it was observed that contractility was dependent on the $Na^+$ electrochemical gradient or the extracellular $Ca^{2+}$ concentration (2 mM, 4 mM). Ryanodine $(10^{-7}\;M)$, the blocker of intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum, did not suppress the development of $Na^+-free$ contracture. The contractile response to norepinephrine $(10^{-6}\;M)$ was augmented by reducing the extracellular $Na^+$ concentration. The relaxation rate from caffeine-induced contraction was dependent on the extracellular $Na^+$ concentration (0 mM, 140 mM). From the above results, it could be suggested that $Na^+/Ca^{2+}$ exchange can move $Ca^{2+}$ either into or out of rabbit basilar arterial smooth muscle. $Ca^{2+}$ entry or extrusion is dependent upon the $Na^+$ electrochemical gradient. $Na^+/Ca^{2+}$ exchange plays a significant role in the regulation of contractility in rabbit basilar arterial smooth muscle.

• The Korean Journal of Pharmacology
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• v.12 no.2 s.20
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• pp.13-19
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• 1976

A fluid extract of Zizyphi Semen was employed in this experiment. The cardiac effects of Zizyphi Semen were examined on isolated rabbits atria and heart in situ of anesthetized cats and rabbits. The adrenergic blocking activity and refractory period of cardiac muscle were measured after administration of this drug. In rabbits and cats the antiarrhythmic action of Zizyphi Semen on atrial and ventricular arrhythmias produced by epinephrine or ouabain was examined. The results were following: 1. Zizyphi Semen produced a decrease in rate and contractile amplitude of the isolated rabbit atria and had a week blocking effect on epinephrine acceleration of atrial movement. 2. Zizyphi Semen effectively abolished the spontaneous arrhythmia occurring in the isolated rabbit atria ana the atrial arrhythmia induced by ouabain. 3. Zizyphi Semen produced a marked prolongation of the refractory period in isolated atrial muscle of rabbit. 4. Zizyphi Semen prevented the induction of ventricular arrhythmia arising from excessive dose of epinephrine in anesthetized rabbits and cats. 5. With regard to the ventricular arrhythmia induced by a continuous infusion of ouabain, Zizyphi Semen exerted suppressive effect and produced a marked prolongation of cardiac arrest time in anesthetized rabbits and cats. From the above results, it may be concluded that Zizyphi Semen is effective against atrial and ventricular arrhythmias. The antiarrhythmic effect of this drug may be the result of direct myocardial depressive and partially adrenergic beta receptor blocking activities including prolongation of the refractory period of cardiac muscle.

• The Journal of Internal Korean Medicine
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• v.19 no.1
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• pp.431-441
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• 1998

This study was undertaken to determine whether Buthus exract(BTE) affects Na^+-K^+-ATPase$ activity of nervous tissues. The enzym activity was measured in synaptosomal fraction prepared from rabbit brain cortex. Na^+-K^+-ATPase$ activity was inhibited by BTE over concentration range of 0.05-0.5% in a dose-dependent manner. The enzyme activity was increased by an increase in $Na^+$ concentration from 5 to 100mM, $K^+$ concentration from 0.5 to 10mM, and $Mg^{2+}$ concentration from 0.2 to 5mM. These changes in ion concentrations did not produce any effect on the inhibitory effect of BTE on $Na^+-K^+-ATPase$ activity. An increase in ATP concentration from 0.1 to 3mM caused an increase in the enzyme activity. The inhibition of the enzyme activity by BTE were not different between two ATP concentrations. A sulfhydryl group protector DTT prevented PCMB-induced inhibition of $Na^+-K^+-ATPase$ activity, but the BTE-induced inhibition was not altered by DTT. The inhibition of enzyme activity by combination of ouabain and BTE was not different from that by Buthus alone. These results suggest that Buthus exerts inhibitory effect on $Na^+-K^+-ATPase$ activity in cerebral synaptosomes, and the action mechansim is similar to that of ouabain.

• Nutrition Research and Practice
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• v.1 no.3
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• pp.200-205
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• 2007

The effects of taurine on plasma and liver cholesterol, erythrocyte ouabain sensitive Na efflux and platelet aggregation were examined in Sprague Dawley rats fed control or 0.5% cholesterol with 0.2% cholate diet. Plasma and liver levels of total cholesterol were increased significantly (p<0.05) in rats fed cholesterol diet compared to the control, and taurine significantly decreased the elevated plasma level of cholesterol in rats fed cholesterol diet (p<0.05). HDL-cholesterol was decreased in groups fed the cholesterol diet regardless of taurine supplementation and the difference between groups with and without cholesterol was significant (p<0.01). Plasma triglyceride was decreased and liver triglyceride was increased both significantly (p<0.05) in rats fed cholesterol compared to the control. Plasma and liver triglyceride in rats fed taurine was decreased significantly compared to the control (p<0.05). Intracellular Na tended to be lower in rats fed cholesterol or taurine and higher in rats fed cholesterol plus taurine compared to the control. Na efflux through Na-K ATPase and the passive leak of Na was somewhat reduced in rats fed cholesterol or taurine and was augmented in rats fed cholesterol plus taurine compared to the control, which showed a similar trend to the intracellular Na. Taurine supplementation caused a suppression of Na efflux in groups fed control diet and restored the suppressed Na efflux in groups fed cholesterol. Platelet aggregation was significantly decreased in the group fed taurine compared to the control (p<0.05) and the group fed cholesterol plus taurine was also a little lower in aggregation than the group fed cholesterol. Microscopic examination showed that taurine prevented fatty liver in rats fed cholesterol diet. Taurine known for stimulating Na-K ATPase in some cell types rather decreased erythrocyte ouabain sensitive Na-K ATPase in the present study. Taurine had hypolipidemic and hypocholesterolemic effects and inhibited platelet aggregation which may be favorable for prevention of cardiovascular diseases.

• The Korean Journal of Physiology
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• v.19 no.2
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• pp.113-125
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• 1985

Electrophysiological difference of the central and peripheral area of the sinoatrial node in the rabbit was studied by glass microelectrode technique. Effects of $K^+,\;Na^+,\;Cs^+,$ adrenaline and ouabain on the action potential of the two areas were investigated, and transient hyperpolarization ($K^+-induced$ hyperpolarization) which developed following readmission of potassium after having pre-treated with $K^+-free$ Tyrode solution for 10 minutes was analyzed. The results obtained were as follows ; 1) The frequency of the spontaneous action potential recorded in the periphery of the SA node was faster than the central area. Reduction by $Cs^+$ and increase by O mM $K^+$, $10^{-6}M$ adrenaline and $10^{-6}M$ ouabain in the frequency of action potential were noticed more prominently in the peripheral than the central area. On the contrary, the frequency in the central area was more decreased than the Peripheral area by 13 mH $K^+$ and 1 mM $Co^{2+}$. 2) The amplitude of the K+_induced hyperpolarization was very small in the central area but large in the peripheral area. Transient hyperpolarization was abolished by ouabain and low sodium, and decreased by cooling the tissue $(17^{\circ}C)$. 3) By changing the concentration of $Ca^{2+}$ in the perfusate, the amplitude and the rate of transient hyperpolarization were increased in the high $Ca^{2+}$ concentration. It could be concluded that the central area of the SA node is less susceptible to the inhibition of Na-Pump and more susceptible to Ca-blocker and high concentration of $K^+$. The Na-Pump activity of the central area measured by means of transient hyperpolarization is found to be much less active than that of the peripheral area.

• The Korean Journal of Pharmacology
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• v.27 no.1
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• pp.53-67
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• 1991

The characteristics and differences between DMPP and McN-A-343 on the secretory effect of catecholamines(CA) were studied in the isolated perfused rat adrenal glands. DMPP(100 uM) and McN-A-343(100 uM) perfused into an adrenal vein of the gland casued significant increases in CA secretion. On molar basis the secretory effect of McN-A-343 was about one fifth as potent as that of DMPP. Tachyphylaxis to releasing effects of CA evoked by DMPP and McN-A-343 was not observed by repeated perfusion of these agents. The DMPP-evoked CA secretion was significantly inhibited by pretreatment with chlorisondamine, desipramine and profusion of $Ca^{2+}-free$ Krebs solution containing EGTA, while it was not affected by pirenzepine, ouabain and physostigmine. However, pretreatment with atropine rather enhanced CA release by DMPP. The releasing effect of CA induced by McN-A-343 was markedly depressed by pretreatment with atropine, pirenzepine, chlorisondamine, physostigmine, and perfusion of $Ca^{2+}-free$ medium plus EGTA but was not influenced by desipramine, except for the case of ouabain which clearly potentiated CA release by McN-A-343. These experimental results suggest that both DMPP and McN-A-343 cause greatly secretion of CA from the isolated perfused rat adrenal glands by a calcium-dependent exocytotic mechanism. The secretory effect of DMPP is due to the stimulation of cholinergic nicotinic receptors and the secretion by McN-A-343 via activation of selecive $M_{1}-muscarinic$ receptors in the adrenal gland. It is also thought that the DMPP-evoked secretory effect is much greater than McN-A-343-induced effect.

• The Journal of Korean Medicine
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• v.16 no.1 s.29
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• pp.281-294
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• 1995

The effect of Sam Hwa San on the Na-K-ATPase activity was evaluated in microsomal fraction prepared from rabbit cerebral cortex to determine whether Sam Hwa San affects Na-K-ATPase activity of nervous system. Sam Hwa San markedly inhibited the Na-K-ATPase activity in a dose-dependent manner with an estimated $I_{50}$ of 0.12%. Optimal pH for the Na-K-ATPase activity was at 7.5 in the presence or absence of Sam Hwa San. The degree of inhibition by the drug more increased at acidic and alkalic pHs than neutral pH. Kinetic studies of substrate and cationic activation of the enzyme indicate classic noncompetitive inhibition fashion for ATP, Na and K, showing significant reduction in Vmax without a change in Km. Dithiothreitol, a sulfhydryl reducing reagent, partially protects the inhibition of Na-K-ATPase activity by Sam Hwa San. Combination of Sam Hwa San and ouabain showed higher inhibition than cumulative inhibition. These results suggest that Sam Hwa San inhibits Na-K-ATPase activity in central nervous system by reacting with, at least a part, sulfhydryl group and ouabain binding site of the enzyme protein, but with different binding site from those of ATP, Na and K.

• The Korean Journal of Pharmacology
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• v.19 no.1
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• pp.101-106
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• 1983

Vanadium is widely distributed in animal tissues and it is supposed to be a regulator of Na-K-ATPase activity. The effect of sodium orthovanadate on Na-K-ATPase activity in rabbit kidney was measured in vitro and compared with that of ouabain. The influence of sodium orthovanadate on the renal function of rabbits was also investigated. 1) Na-K-ATPase activity was decreased by sodium orthovandate at the concentrations of $10^{-7},\;10^{-6},\;10^{-5}\;and\;10^{-4}\;M$ to 73.89, 36.49, 6.50 and 4.99% of the control activity respectively. 2) Na-K-ATPase activity was decreased by ouabain at the concentrations of $10^{-4},\;10^{-3}\;and\;10^{-2}\;M$ to 69.52, 22.84 and 3.88% of the control activity respectively. 3) Urine volume, urinary excretion of $Na^+,\;K^+\;and\;Cl^-$, clearances of inulin and p-amino-hoppuric acid were decreased until after 60 minutes following the administration of sodium orthovanadate 0.5 mg/kg intravenously $Na^+\;reasorption$ rate was not changed and mean arterial pressure was significantly elevated during 60 minutes after the administration of sodium orthovanadate.

• The Korean Journal of Physiology
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• v.8 no.1
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• pp.67-76
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• 1974

The effect of saponin on the sodium plus potassium activated ATPase activity was studied in the rabbit red cell ghosts and the experiments were also designed to determine the mechanism of action of saponin on the APTase activity. The following results were observed. 1. The ATPase activity of rabbit red cell ghosts is inhibited by low concentration of saponin but increased by high concentration. The activating effect of saponin on the $Na^{+}-K^{+}-ATPase$ activity is inhibited by ouabain but the stimulation of the $Mg^{++}-ATPase$ by high concentration of saponin is not inhibited by ouabain. 2. The activity ratio of $Na^{+}-K^{+}-ATPase$ by high concentration of saponin is decreased by raising the potassium concentration, and is increased by raising the sodium concentration. 3. The ATPase activity is increased by small amounts of calcium but inhibited by larger amounts. The activity ratio of the enzyme by saponin is decreased by raising the calcium concertration 4. The action on the ATPase activity was not related to the amino group of lysine, the hydroxyl group of threonine, the imidazole group of histidine, or the carboxyl group of aspartic acid. 5. The action of saponin on the ATPase activity is due to sulfhydryl group of the enzyme of $Na^{+}-K^{+}-ATPase$.

• YAKHAK HOEJI
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• v.31 no.6
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• pp.376-393
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• 1987

This study was performed in order to investigate the effect of nifedipine, a vasodilating drug which acts through calcium antagonism, on renal function using mongrel dog. Nifedipine, when given interavenously in doses ranging from 1.5 to 5.0$\mu\textrm{g}$/kg, elicited diuresis along with less changes of glomerular filtration rate and significant increases of renal plasma flow, so that the filtration fraction(FF) decreased significantly, at the same time both osmolar and free water clearances increased, and amount of sodium, potassium and calcium excreted in urine increased significantly. Nifedipine, when infused into a renal artery in doses from 0.05 to 0.15$\mu\textrm{g}$/kg/min, exhibited identical responses to the actions of intraveneous nifedipine except significant increase of glomerular filtration rate and no change of FF, which was confined only to the infused kidney. The renal action of nifedipine into a renal artery were not influenced by renal denervation, decreased significantly by ouabain, Na$^+$-K$^+$-ATPase inhibitor, which was given into a renal artery. Nifedipine infused into a renal artery in dog pretreated with propranolol i.v. produced diuresis associated with the increase of electrolytes excretion by reduction of electrolyte reabsorption and with no changes of glomerular filtration rate and renal plasma flow. Thus, it is concluded that nifedipine infused into a renal aretery produces diuretic action along with both improvement of hemodynamics and inhibition of electrolytes reabsorption, which may be related to sympathetic $\beta$-receptor or Na$^+$-K$^+$-ATPase activity because the action of nifedipine in kidney is blocked by propranolol or ouabain.