• Biomolecules & Therapeutics
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• 제5권3호
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• pp.228-232
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• 1997

AU-164 was synthesized as a reversible gastric $H^+/K^+$ ATPase inhibitor, and its effects were tested in various systems. AU-164 inhibited rabbit gastric $H^+/K^+$ ATPase with an $IC_{50}$/ of 9 $\mu$M. On the other hand, AU-164 was a weak inhibitor for dog kidney $Na^+/K^+$ ATPasc, indicating the selectivity for gastric $H^+/K^+$ ATPase. The reversible property of the AU-164-induced inhibition of $H^+/K^+$ ATPase was confirmed by filtering the inhibition mixture through Sephadex G-25M column. In vivo basal acid secretion was also inhibited by AU-164 under the pylorus ligation of Sprague-Dawley rats. In addition, AU-164 protected dose dependently gastric lesion induced by ethanol in rats. The $ED_{50}$ value of 62 mg/kg p.o was estimated. These results suggest that AU-164 is a potent, selective and reversible gastric $H^+/K^+$ ATPase inhibitor, and that AU-164 has a potential use for the clinical therapeutics of peptic ulcer disease.

• 한국동물학회지
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• 제15권4호
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• pp.163-182
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• 1972

토끼의 골격근 小胞體의 ATPase 活性과 Ca吸收能에 미치는 caffeine의 영향을 조사 하였다. 遠心分離로 分劃된 小胞體에서 $2,000 \\sim 8,000 \\times G$ 分劃의 ATPase 活性은 caffeine에 의하여 增大되지만 $8,000 \\times G$ 以上의 分劃에서는 아무 영향도 받지 않았다. Caffeine에 의한 이 活性增大는 이 分劃에 混在하는 mitochondria의 ATPase 活性이 增大 된 結果라고 해석된다. 小胞體의 $2,000 \\sim 10,000 \\times G$ 分劃과 $10,000 \\sim 20,000 \\times G$ 分劃의 Ca吸收能도은 反應液內 Ca의 농도가 200 nmoles/mg protein 정도 이상일 때는 caffeine에 의하여 현저히 阻害되지만, Ca의 농도가 이 以上이 때는 2,000$\\sim$10,000 分劃에서만 이 阻害現象을 볼 수 있다. 低農度 Ca에서의 이 阻害現象은 caffeine에 의하여 mitochondira의 Ca吸收도 阻害되기 때문에 나타나는 것으로 해석된다. Caffiene에 의한 筋收縮의 誘發 및 逕縮現象은 筋小胞體의 Ca 吸收가 이 特質에 의하여 阻害되고 또 蓄積된 Ca이 放出되기 때문에 일어나는 것으로 해석된다.

• Archives of Pharmacal Research
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• 제19권2호
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• pp.126-131
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• 1996

The effects of various synthetic benzimidazole derivatives on gastric H^+/K^+$ATPase activity in vitro were examined. The results showed that the effects of substituents on the benzimidazole ring were not significant. However, replacement of sulfoxide connecting two ring systems to sulfide resulted in a completely inactive compound in vitro, suggesting the essential role of sulfoxide group in the inhibition. In addition, compounds with 5 or 6-membered oxacyclic substituents attached to the pyridine ring displayed the most effective inhibitory activity. Among these derivatives, AU-47 was the most potent, and detailed mechanistic studies with the compound were carried out. AU-47 inhibited gastricH^+/K^+$ATPase in a concentration and time dependent manner with 50% inhibition at $6\muM$. The presence of sulfhydryl reducing agents or substrate analogue protected H^+/K^+$ATPase from the inactivation. The inhibition by AU-47 was potentiated by acid pretreatment of the compound, suggesting the structural conversion of AU-47 into a more active intermediate which was favored in acidic condition. Consistent with in vitro results, AU-47 inhibited in vivo gastric acid secretion. The results suggest that AU47 is a relevant candidate for the development of new antiulcer agent.

• Journal of Acupuncture Research
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• 제18권2호
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• pp.150-160
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• 2001

Objectives ; This study was undertaken to determine whether Carthami-Flos aquacapuncture (CFA) exerts protective effect against oxidant-induced inhibition of $Na^+-K^+$-ATPase activity in cerebral synaptosomes. Methods and Results ; The enzyme activity was dependent on incubation time and enzyme protein concentrations. An oxidant t-butylhydroperoxide (tBHP) at 1 mM concentration caused a significant inhibition of $Na^+-K^+$-ATPase activity, which was prevented by addition of 0.01% CFA. tBHP inhibition and CFA protection were independent on incubation time or enzyme protein concentrations. The enzyme activity was increased by ATP in a dose dependent manner. Effects of tBHP and CFA were not affected by ATP cocentrations. tBHP (1 mM) produced a significant increase in lipid peroxidation in cerebral synaptosomes, which was prevented by 0.01% CFA. CFA decreased oxygen free radicals generated induced by the phorbol-ester in a dose-dependent manner in human neutrophil. Conclusions ; These results suggest that CFA exerts protective effect against tBHP-induced inhibition of $Na^+-K^+$-ATPase activity, which is due to by an antioxidant action resulting from a direct scavenging effect of oxygen free radicals in the cerebral synaptosomes.

• The Korean Journal of Physiology
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• 제6권1호
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• pp.27-31
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• 1972

The activity of Mg and Na-K activated ATPase of homogenate from rat brain cortex was measured in vitro under the variety of conditions. The effects of various hypnotic and tranquilizer such as phenobarbital, amobarbital, diazepam, promazine and chlorpromazine on the activities of both ATPase was investigated and the results was summarized as follows. 1. Na-K ATPase was slightly inhibited by phenobarbital and amobarbital while Mg ATPase was moderately activated by these drugs. 2. Both Mg and Na-K ATPase activities were markedly inhibited by diazepam. 3. Promazine and chlorpromazine markedly inhibited both Mg and Na-K ATPase activities. These findings indicate that remarkable correlation between hypnotic or tranquilizing potency and ATPase inhibition could be observed.

• 한국미생물·생명공학회지
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• 제27권5호
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• pp.354-358
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• 1999

In order to know the antifungal characteristics of saturated fatty acids having 6 to 12 carbons, their minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) were estimated against Saccharomyces cerevisiae. Fatty acids from C6 to C11 exhibited increasing activity with chain length, but C12 fatty acid did not show activity at all. In relation to antifungal modes of actions, fatty acids investigated showed on inhibitory activity toward the plasma membrane H+-ATPase of Saccharomyces cerevisiae. Their inhibitions to the glucose-induced acidification and ATP hydrolysis caused by the proton pump were found to be in common wiht antifungal activities. At the test concentration of 1mM, hexanoic acid (C6) showed the lowest inhibition of about 30%, while undecanoic acid(C11) showed the strongest inhibition of over 90%. In addition, as seen with antifungal activity, the inhibitory activity of dodecanoic acid (C12) was suddenly reduced to less than 50%.

• Applied Biological Chemistry
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• 제44권2호
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• pp.67-72
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• 2001

식물 뿌리세포의 원형질막 및 액포막에 위치하는 $H^+-ATPase$들은 세포의 여러 가지 생리활성에 중요한 역할을 수행한다. $H^+-ATPase$의 생리활성 특성을 조사하기 위하여 토마토 뿌리조직으로부터 마이크로솜을 분리하고, $H^+-ATPase$의 활성에 미치는 음이온의 효과를 조사하였다. 다양한 종류의 음이온들이 $H^+-ATPase$의 활성을 저해함을 확인하였으며, 이들 중 특히 효소의 저해정도가 다른 citrate와 인산을 선택하여 작용특성을 조사하였다. Citrate에 의한 ATPase활성저해는 3 mM 이상에서 나타났고, 20 mM citrate는 활성을 50-60% 저해하였다. 그러나, citrate의 저해효과는 $Mg^{2+}$의 농도를 증가시킬수록 감소하여, citrate에 의해 저해된 ATPase 활성은 $Mg^{2+}$에 의해 회복되는 것으로 나타났다. 즉, 7 mM $Mg^{2+}$을 첨가하였을 때, citrate에 의한 활성저해는 관측되지 않았고 ATPase활성은 대조활성과 비슷한 수준으로 회복되었다. 이러한 결과로 부터 citrate는 Mg^{2+}을 chelation함으로써$H^+-ATPase$의 활성을 저해함을 확인하였다. 한편, 인산에 의한 ATPase활성저해는 3 mM 이상의 농도에서 나타났고, 30 mM 인산은 ATPase의 활성을 50% 저해하였다. 인산에 의해서 저해된 ATPase의 활성은 $Mg^{2+}$니 농도증가에 의해 회복되지 않아, 인산에 의한 저해효과는 $Mg^{2+}$과 무관하였다.

• 동국한의학연구소논문집
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• 제8권1호
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• pp.93-106
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• 1999

우리나라와 같이 B형 간염 바이러스의 유병율이 높은 지역에서는 B형 간염 바이러스뿐만 아니라 HCV에 대한 항 바이러스 효과도 동시에 시행함이 유용할 것으로 사료되었다. 본 연구에서는 인진청간탕(菌蔯淸肝湯)을 이용하여 B형 간염 바이러스에 대한 항(抗) 바이러스 효과를 PCR을 이용하여 HBV의 DNA를 검색하였다. 인진청간탕(菌蔯淸肝湯)이 처리된 처리군의 경우 대조군에 비하여 농도 의존적으로 B형 간염 바이러스의 표면항원 생산을 억제하였고, PCR을 이용하여 증폭한 경우에도 증폭된 DNA의 양은 감소하였다. 또한 C형 간염 바이러스에 대한 항(抗) 바이러스 효과를 검색하기 위하여 복제에 필수적인 단백질인 HCV helicase의 ATPase에 대한 활성 억제 효과를 조사하였다. 인진청간탕(菌蔯淸肝湯)이 HCV helicase의 ATPase 활성을 억제하는 효과가 있음을 확인한 후 dose-respond에 따른 실험을 수행하여 HCV helicase의 ATPase 활성을 억제함으로써 탈인산화 되지 않은 ATP의 양을 이용하여 PSL로 분석한 결과 인진청간탕(菌蔯淸肝湯)이 HCV helicase의 ATPase 기능에 대한 억제효과가 우수함이 확인되었다. 이상의 결과로 보아 인진청간탕(菌蔯淸肝湯)이 B형 및 C형 간염치료에 동시에 응용될 수 있을 것으로 사료된다.

• 대한약리학회지
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• 제30권1호
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• pp.117-124
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• 1994

Phospholamban은 심근 근장그물 $Ca^{2+}-ATPase$ 조절단백이다. 조절작용기전은 탈인산화된 phospholamban에 의해 $Ca^{2+}-ATPase$가 억제됨으로 나타나며, 이 phospholamban이 인산화됨으로 $Ca^{2+}-ATPase$에 대한 억제가 반전됨을 보인다. 최근에 phospholamban의 cytoplasmic domain만으로 $Ca^{2+}-ATPase$를 억제하기에는 불충분하다는 보고가 있어 본 실험을 계획하였다. $Ca^{2+}-ATPase$의 활성을 억제하는 phospholamban domain을 밝히기 위하여 합성한 phospholamban 펩타이드(아미노산 1-25)의 $Ca^{2+}$ uptake에 대한 효과를 살펴보았다. 골격근 근장그물에서 $Ca^{2+}-ATPase$를 분리한 후 phosphatidylcholine이나 phosphatidylcholine과 phosphatidylserine을 포함한 liposome에 재조합시켰다. Phospholamban 펩타이드는 phosphatidylcholine을 이용하여 재조합된 vesicles의 초기 $Ca^{2+}$ uptake rate를 억제하고, cAMP 의존성 protein kinase의 catalytic subunit로 인산화시킨 phospholamban 펩타이드는 이 억제를 반전시킴을 보여 주었다. Phosphatidylcholine과 phosphatidylserine을 포함한 제조합 vesicles에서도 같은 양상을 보였다. 이상의 결과로 미루어 볼 때 인산화 sites를 포함하고 있는 phospholamban의 cytoplasmic domain은 그 자체만으로도 근장그물 칼슘펌프를 억제하기에 충분하다고 결론지을 수 있다.

• The Korean Journal of Physiology and Pharmacology
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• 제4권1호
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• pp.63-72
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• 2000

Chronic exposure to cadmium (Cd) results in an inhibition of protein endocytosis in the renal proximal tubule, leading to proteinuria. In order to gain insight into the mechanism by which Cd impairs the protein endocytosis, we investigated the effect of Cd on the acidification of renal cortical endocytotic vesicles (endosomes). The endosomal acidification was assessed by measuring the pH gradient-dependent fluorescence change, using acridine orange or FITC-dextran as a probe. In renal endosomes isolated from Cd-intoxicated rats, the $V_{max}$ of ATP-driven fluorescence quenching ($H^+-ATPase$ dependent intravesicular acidification) was significantly attenuated with no substantial changes in the apparent $K_m,$ indicating that the capacity of acidification was reduced. When endosomes from normal animals were directly exposed to free Cd in vitro, the $V_{max}$ was slightly reduced, whereas the $K_m$ was markedly increased, implying that the biochemical property of the $H^+-ATPase$ was altered by Cd. In endosomes exposed to free Cd in vitro, the rate of dissipation of the transmembrane pH gradient after $H^+-ATPase$ inhibition appeared to be significantly faster compared to that in normal endosomes, indicating that the $H^+-conductance$ of the membrane was increased by Cd. These results suggest that in long-term Cd-exposed animals, free Cd ions liberated in the proximal tubular cytoplasm by lysosomal degradation of cadmium-metallothionein complex (CdMT) may impair endosomal acidification 1) by reducing the $H^+-ATPase$ density in the endosomal membrane, 2) by suppressing the intrinsic $H^+-ATPase$ activity, and 3) possibly by increasing the membrane conductance to $H^+$ ion. Such effects of Cd could be responsible for the alterations of proximal tubular endocytotic activities, protein reabsorption and various transporter distributions observed in Cd-exposed cells and animals.