• Archives of Pharmacal Research
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• v.28 no.3
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• pp.269-273
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• 2005

A furocoumarin derivative, psoralen (7H-furo[3,2-g][1]benzopyran-7-one), was isolated from the n-hexane fraction of Heracleum moellendorffii Hance. We examined the effects of psor-alen on a human Kv1.5 potassium channel (hKv1.5) cloned from human heart and stably expressed in Uk- cells. We found that psoralen inhibited the hKv1.5 current in a concentration-, use- and voltage-dependent manner with an IC$_{50}$ value of 180 $\pm$ 21 nM at +60 mV. Psoralen accelerated the inactivation kinetics of the hKv1.5 channel, and it slowed the deactivation kinetics of the hKv1.5 current resulting in a tail crossover phenomenon. These results indicate that psoralen acts on the hKv1.5 channel as an open channel blocker. Furthermore, psoralen prolonged the action potential duration of rat atrial muscles in a dose-dependent manner. Taken together, the present results strongly suggest that psoralen may be an ideal antiarrhythmic drug for atrial fibrillation.

• Archives of Pharmacal Research
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• v.29 no.10
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• pp.834-839
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• 2006

Torilin was purified from Torilis japonica (Houtt.) DC., and its effects on a rapidly activating delayed rectifier $K^+$ channel (hKv1.5), cloned from human heart and stably expressed in Ltk cells, as well as the corresponding $K^+$ current (the ultrarapid delayed rectifier, $I_{KUR}$) were assessed in human atrial myocytes. Using the whole cell configuration of the patch-clamp technique, torilin was found to inhibit the hKv1.5 current in time and voltage-dependent manners, with an $IC_50$ value of $2.51{\pm}0.34\;{\mu}M$ at +60 mV. Torilin accelerated the inactivation kinetics of the hKv1.5 channel, and slowed the deactivation kinetics of the hKv1.5 current, resulting in a tail crossover phenomenon. Additionally, torilin inhibited the hKv1.5 current in a use dependent manner. These results strongly suggest that torilin is a type of open-channel blocker of the hKv1.5 channel.

• Bulletin of the Korean Chemical Society
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• v.29 no.1
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• pp.43-46
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• 2008

The aim of present study was to examine the inhibitory effects of hydroxamic acid derivatives on the melanogenesis. We found that hydroxamic acid moiety was important for anti-melanogenic activity. Compounds 1a and 1b strongly inhibited melanin synthesis via deactivation of tyrosinase. Hydroxamic acid has metal ion chelating ability which is similar to that kojic acid, however, anti-tyrosinase mechanism of compounds 1a and 1b was different from that of kojic acid. They showed noncompetitive inhibition kinetics

• Journal of Microbiology and Biotechnology
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• v.11 no.4
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• pp.598-606
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• 2001

A mathematical model is proposed that can depict the kinetics of simultaneous saccharification and fermentation (SSF) using steam-exploded wood(SEW) with a glucose- and cellobiose-fermenting yeast strain. Brettanomyces custersii. An expression to describe the reduction of the relative digestibility during the hydrolysis of the SEW is introduced in the hydrolysis model. The fermentation model also takes two new factors into account, that is, the effects of the inhibitory compounds present in the SEW hydrolysates on the microorganism and the fermenting ability of Brettanomyces custersii, which can use both glucose and cellobiose as carbon sources. The model equations were used to simulate the hydrolysis of the SEW, the fermentation of the SEW hydrolysates, and a batch SSF, and the results were compared with the experimental data. The model was found to be capable of representing ethanol production over a range of substrate concentrations. Accordingly, the limiting factors in ethanol production by SSF under the high concentration of the SEW were identified as the effect of inhibitory compounds present in the SEW, the enzyme deactivation, and a limitation in the digestibility based on the physical condition of the substrate.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.5
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• pp.461-469
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• 1999

Glutamate and ${\gamma}-aminobutyric$ acid (GABA) are major excitatory and inhibitory neurotransmitters in the vertebrate retina, respectively. Using the whole-cell patch clamp technique and a rapid solution changer, glutamate and GABA receptors have been extensively investigated in carp retina. Glutamate receptors on both horizontal and amacrine cells may be an AMPA preferring subtype, which predominantly consists of flop splice variants. $GABA_A$ and $GABA_C$ receptors coexist in bipolar cells and they both show significant desensitization. Kinetics analysis demonstrated that activation, deactivation and desensitization of the $GABA_C$ receptor-mediated response of these cells are overall slower than those of the $GABA_A$ response. Endogenous modulator $Zn^{2+}$ in the retina was found to differentially modulate the kinetic characteristics of the $GABA_C$ and $GABA_A$ responses.

• The Korean Journal of Physiology and Pharmacology
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• v.26 no.2
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• pp.135-144
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• 2022

An antidiabetic drug, rosiglitazone is a member of the drug class of thiazolidinedione. Although restrictions on use due to the possibility of heart toxicity have been removed, it is still a drug that is concerned about side effects on the heart. We here examined, using Chinese hamster ovary cells, the action of rosiglitazone on Kv1.5 channels, which is a major determinant of the duration of cardiac action potential. Rosiglitazone rapidly and reversibly inhibited Kv1.5 currents in a concentrationdependent manner (IC₅₀ = 18.9 μM) and accelerated the decay of Kv1.5 currents without modifying the activation kinetics. In addition, the deactivation of Kv1.5 current, assayed with tail current, was slowed by the drug. All of the results as well as the usedependence of the rosiglitazone-mediated blockade indicate that rosiglitazone acts on Kv1.5 channels as an open channel blocker. This study suggests that the cardiac side effects of rosiglitazone might be mediated in part by suppression of Kv1.5 channels, and therefore, raises a concern of using the drug for diabetic therapeutics.

• The Korean Journal of Physiology and Pharmacology
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• v.27 no.1
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• pp.95-103
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• 2023

Rosiglitazone is a thiazolidinedione-class antidiabetic drug that reduces blood glucose and glycated hemoglobin levels. We here investigated the interaction of rosiglitazone with Kv3.1 expressed in Chinese hamster ovary cells using the wholecell patch-clamp technique. Rosiglitazone rapidly and reversibly inhibited Kv3.1 currents in a concentration-dependent manner (IC₅₀ = 29.8 µM) and accelerated the decay of Kv3.1 currents without modifying the activation kinetics. The rosiglitazonemediated inhibition of Kv3.1 channels increased steeply in a sigmoidal pattern over the voltage range of -20 to +30 mV, whereas it was voltage-independent in the voltage range above +30 mV, where the channels were fully activated. The deactivation of Kv3.1 current, measured along with tail currents, was also slowed by the drug. In addition, the steady-state inactivation curve of Kv3.1 by rosiglitazone shifts to a negative potential without significant change in the slope value. All the results with the use dependence of the rosiglitazone-mediated blockade suggest that rosiglitazone acts on Kv3.1 channels as an open channel blocker.

• Food Science and Biotechnology
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• v.18 no.3
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• pp.661-666
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• 2009

The heat tolerance and the inactivation kinetics of peroxidase (POD) and polyphenol oxidase (PPO) in pineapples (Ananas comosus) were studied in the temperature range $45-95^{\circ}C$. The kinetic parameters, such as deactivation rate constant (k), activation energy ($E_a$), and decimal reduction rate (D) of the thermal inactivation process, were determined. POD in pineapples showed biphasic inactivation behavior at temperatures range $45-75^{\circ}C$ but was monophasic at $85-95^{\circ}C$. This indicate that POD has 2 isozymes, namely heat labile and heat resistant, with $E_a$ of 68.79 and 93.23 kJ/mol, respectively. On the other hand, the heat denaturation of pineapple PPO could be described as simple monophasic first-order behavior with $E_a$ of 80.15 kJ/mol. Thus, the results of this study is useful in blanching technology where it shows a shortened time with higher temperature can be applied. The determination of the heat tolerance and inactivation POD and PPO, at different temperature range as done in the present work, was very important to improve the blanching process. This also will help to optimize the pineapple canning process which is one of the most important food industries in many tropical regions.

• Journal of Microbiology and Biotechnology
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• v.13 no.5
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• pp.717-724
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• 2003

A newly isolated Citrobacter sp. Y19 catalyzes the CO-dependent $H_2$ production (biological water-gas shift reaction) by the actions of CO dehydrogenase (CODH) and hydrogenase. Y 19 requires $O_2$ for fast growth, but its $H_2$ production activity is significantly inhibited by $O_2$. In the present study, the effect of $O_2$ on the activities of CODH ard hydrogenase was investigated quantitatively in both whole cells and broken cells, based on CO-dependent or methyl viologen (MV)-dependent $H_2$ production in addition to CO-dependent MV reduction. In crude cell extracts, CODH activity was mostly found in the soluble fraction. Inactivation of CODH and hydrogenase activities by $O_2$ followed the first-order decay kinetics, and the dependence of the rate constants on $O_2$ partial pressure could be expressed by the Michaelis-Menten equation. In whole cells, the maximum deactivation rate constants ($k_{d,max}$ of hydrogenase and CODH were quite similar: $0.07{\pm}0.03 min^{-1}\;and\;0.10{\pm}0.04 min^{-1}$, respectively. However, the first-order rate constant ($k_{d,max}/K_s$) of CODH ($0.25\;min^{-1}\;atm^{-1}$) at low $O_2$ partial pressures was about 3-fold higher than that of the hydrogenase, since the half-saturation constant ($K_s$) of CODH was about half of that of hydrogenase. In broken cells, both enzymes became significantly more sensitive to $O_2$ compared to the unbroken cells, while $k_{d,max}/K_s$ increased 37-fold for hydrogenase and 6.7-fold for CODH. When whole cells were incubated under anaerobic conditions after being exposed to air for 1 h, hydrogenase activity was recovered more than 90% in 2 h suggesting that the deactivation of hydrogenase by $O_2$ was reversible. On the contrary, CODH activity was not recovered once deactivated by $O_2$ and the only way to recover the activity was to synthesize new CODH. This study indicates that $O_2$ sensitivity of $H_2$ production activity of Citrobacter sp. Y19 is an important drawback as in other $H_2-producing$ bactria.

• Journal of the Korean Chemical Society
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• v.33 no.2
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• pp.168-176
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• 1989

Theoretical analysis of HF chemical laser models are performed through chemical reaction kinetics, gain process and stimulated emission process. A chemical laser of F+$H_2$ nonchain reaction is investigated through V-R transitions of excited HF for vibrational levels up to v = 3 and rate equations including nonchain pumping and deactivation. On this analysis, harmonic and anharmonic vibrational levels are considered separately and the results of the corresponding power calculations are showed very small difference between the two. Output powers are calculated with variation of temperature and initial concentrations of $H_2$. A HF chemical laser of $H_2$+$F_2$ chain reaction is also simulated with a premixed initial condition. Results of present model calculations are satisfactory through comparison with detailed calculations reported by others.