• The Korean Journal of Physiology
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• v.19 no.1
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• pp.49-59
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• 1985

The effects of anions on net accumulation of $(\rho-aminohippuric\;acid)$(PAH) were studied in rabbit kidney cortical slices. Experiments were carried while varying the major anionic composition of the incubation medium(replacement of $Cl^-$ by isethionate and $SCN^-$). The total replacement of $Cl^-$ with isethionate, $SO_4\;^{2-}$ and $SCN^-$ in the incubation medium decreased the 60-min slice-to-medium concentration(S/M) ratio of PAH to 60%, 40% and 50% of control value, respectively. The degree of inhibition in PAH accumulation by the replacement of isethionate and $SCN^-$ was increased with increasing of both preincubation and incubation time. The influence of isethionate and $SCN^-$ on PAH uptake was fully reversible. Both isethionate and $SCN^-$ increased the apparent Km value significantly with no change on the apparent Vmax value, suggesting a competitive inhibition on PAH uptake. And the inhibitory effect of $SCN^-$ on PAH uptake decreased with increase of pH in the incubation medium while that of isethionate increased with increase of pH. Intracellular water content, intracellular electrolyte concentration and oxygen consumption were not influenced by the replacement of $Cl^-$ with isethionate or $SCN^-$ in the incubation medium. These results suggest that both $isethionate^-$ and $SCN^-$ inhibit the PAH uptake by binding to some site necessary for normal PAH transport without affecting the cellular viability.

• Proceedings of the KSAR Conference
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• 2003.06a
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• pp.61-61
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• 2003

We have investigated the novel function of tissue transglutaminase (tTG) in the germinal vesicle breakdown (GVBD) of mouse oocyte. tTG was identified in ooplasm and germinal vesicle by immunostaining assay. Spontaneous maturation of the oocytes elevated in situ activity of tTG by over 2.5 fold at 3 hr, which was determined by a confocal microscopic assay. However, incubation with monodansylcadaverine (MDC), a tTG inhibitor, blocked the activation of tTG. The possible role of tTG in GVBD was investigated by the use of two tTG inhibitors, MDC and cystamine. MDC largely inhibited the GVBD by a concentration dependent manner. GV-stage oocytes were matured to the GVBD stage by 78% at 3 hr in BWW culture medium. However, in the oocytes incubated with MDC for 3 hr, the GVBD rates were 43 and 11% by 50 and 100 mM, respectively. MDC also blocked the entry of 70 kDa TRITC-dextran from the ooplasm to the compartment of germinal vesicle, indicating a possible inhibition of nuclear pore disassembly by MDC. The role of tTG in GVBD was further investigated by microinjection with cystamine. The control oocytes, injected with DPBS, showed about 80 % of GVBD at 3 hr. But the oocytes injected with cystamine showed 15% of GVBD at 3 hr and a little higher rate at 6 hr. In addition, the inhibition of GVBD maturation by MDC was reversible by washing. These results suggested that tTG was involved in the early event of mouse oocyte maturation

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.5
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• pp.485-493
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• 1997

We investigated the effect of ${\alpha}-adrenergic$ and cholinergic receptor agonists on $Ca^{2+}$ current in adult rat trigeminal ganglion neurons using whole-cell patch clamp methods. The application of acetylcholine, carbachol, and oxotremorine ($50\;{\mu}M\;each$) produced a rapid and reversible reduction of the $Ca^{2+}$ current by $17{\pm}6%,\;19{\pm}3%,\;and\;18{\pm}4%$, respectively. Atropine, a muscarinic antagonist, blocked carbachol- induced $Ca^{2+}$ current inhibition to $3{\pm}1%$. Norepinephrine ($50\;{\mu}M$) reduced $Ca^{2+}$ current by $18{\pm}2%$, while clonidine ($50\;{\mu}M$), an ${\alpha}2-adrenergic$ receptor agonist, inhibited $Ca^{2+}$ current by only $4{\pm}1%$. Yohimbine, an ${\alpha}2-adrenergic$ receptor antagonist, did not block the inhibitory effect of norepinephrine on $Ca^{2+}$ current, whereas prazosin, an ${\alpha}1-adrenergic$ receptor antagonist, attenuated the inhibitory effect of norepinephrine on $Ca^{2+}$ current to $6{\pm}1%$. This pharmacology contrasts with ${\alpha}2-adrenergic$ receptor modulation of $Ca^{2+}$ channels in rat sympathetic neurons, which is sensitive to clonidine and blocked by yohimbine. Our data suggest that the modulation of voltage dependent $Ca^{2+}$ channel by norepinephrine is mediated via an α1-adrenergic receptor. Pretreatment with pertussis toxin (250 ng/ml) for 16 h greatly reduced norepinephrine- and carbachol-induced $Ca^{2+}$ current inhibition from $17{\pm}3%\;and\;18{\pm}3%\;to\;2{\pm}1%\;and\;2{\pm}1%$, respectively. These results demonstrate that norepinephrine, through an ${\alpha}1-adrenergic$ receptor, and carbachol, through a muscarinic receptor, inhibit $Ca^{2+}$ currents in adult rat trigeminal ganglion neurons via pertussis toxin sensitive GTP-binding proteins.

• Biomolecules & Therapeutics
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• v.3 no.3
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• pp.205-209
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• 1995

The novel compound KH 3218 was synthesized and evaluated for its ability to inhibit the gastric H$^{＋}$＋ $K^{＋}$ ATPase activity in vitro as well as to lessen gastric acid secretion in vivo. KH 3218 inhibited rabbit gastric H$^{＋}$＋ $K^{＋}$ ATPase in a concentration and time dependent manner. $IC_{50}$/ value was estimated to be about 15 $\mu$M. The inhibition of the H$^{＋}$＋ $K^{＋}$ ATPase by KH 3218 was blocked by sulfhydryl reducing agents, dithiothreitol or $\beta$-mercaptoethanol. The inhibition of the enzyme was not reversible by 50 fold dilution of the incubation mixtures, suggesting the irreversible nature of the inactivation. In the pylorus-ligated rift, KH 3218 reduced the total acid output as compared with the control. In addition, KH 3218 was capable of inhibiting H. pylori urease activity. These data suggest that KH 3218 is a potent inhibitor for H$^{＋}$＋ $K^{＋}$ ATPase activity as well as for gastric acid secretion, and has a potential to be developed as a novel antiulcer agent.

• The Korean Journal of Physiology and Pharmacology
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• v.24 no.3
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• pp.193-201
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• 2020

Chromosomal region maintenance 1 (CRM1) is associated with an adverse prognosis in glioma. We previously reported that CRM1 inhibition suppressed glioma cell proliferation both in vitro and in vivo. In this study, we investigated the role of CRM1 in the migration and invasion of glioma cells. S109, a novel reversible selective inhibitor of CRM1, was used to treat Human glioma U87 and U251 cells. Cell migration and invasion were evaluated by wound-healing and transwell invasion assays. The results showed that S109 significantly inhibited the migration and invasion of U87 and U251 cells. However, mutation of Cys528 in CRM1 abolished the inhibitory activity of S109 in glioma cells. Furthermore, we found that S109 treatment decreased the expression level and activity of MMP2 and reduced the level of phosphorylated STAT3 but not total STAT3. Therefore, the inhibition of migration and invasion induced by S109 may be associated with the downregulation of MMP2 activity and expression, and inactivation of the STAT3 signaling pathway. These results support our previous conclusion that inhibition of CRM1 is an attractive strategy for the treatment of glioma.

• Journal of Photoscience
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• v.9 no.2
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• pp.90-93
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• 2002

Phytochrome A (phyA) and phytochrome B (phyB) perceive light and adapt to fluctuating circumstances by different manners in terms of effective wavelengths, required fluence and photoreversibility. Action spectra for induction of seed germination and inhibition of hypocotyl elongation using phytochrome mutants of Arabidopsis showed major difference. PhyA is the principal photoreceptor for the very low fluence responses and the far-red light-induced high irradiance responses, while phyB controls low fluence response in a red/far-red reversible mode. The structural requirement of their bilin chromophores for photosensory specificity of phyA and phyB was investigated by reconstituting holophytochromes through feeding various synthetic bilins to the following chromophore-deficient mutants: hy1, hyl/phyA and hyl/phyB mutants of Arabidopsis. We found that the vinyl side-chain of the D-ring in phytochromobilin interacts with phyA apoprotein. This interaction plays a direct role in mediating the specific photosensory function of phyA. The ethyl side-chain of the D-ring in phycocyanobilin fails to interact with phyA apoprotein, therefore, phyA specific photosensory function is not observed. In contrast, both phytochromobilin and phycocyanobilin interact with phyB apoprotein and induce phyB specific photosensory functions. Structural requirements of the apoproteins and the chromophores for the specific photoperception of phyA and phyB are discussed.

• Transactions of the Korean hydrogen and new energy society
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• v.26 no.6
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• pp.532-540
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• 2015

Electrochemical alane ($AlH_3$) production process can be provided as a synthesis route which close a reversible cycle. In this study, growth inhibition of dendrite as key issues in this process was investigated. Main cause of dendrite growth was because Al fine powder separated in consumption process of Al electrode was moved to Pd electrode. In an effort to avoid this, use of glass block with uniform holes was the most effective to inhibit the amount of dendrite to that of $AlH_3$. Furthermore, effects of Al electrode (anode) type and electrolyte concentration were investigated and the optimal condition for inhibiting dendrite formation was proposed.

• Reproductive and Developmental Biology
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• v.31 no.2
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• pp.71-76
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• 2007

Previous studies have shown that BMI-1026 is a potent inhibitor of the cyclin-dependent kinases (cdk). In cell culture, the compound also arrests G2/M strongly and G1/S and S weakly. Two key kinases, cdk1 (p34cdc2 kinase) and mitogen-activated protein (MAP) kinase (erk1 and 2), perform crucial roles during oocyte maturation and, later, metaphase II (MII) arrest. In mammalian oocytes, both kinases are activated gradually around the time of germinal vesicle breakdown (GVBD) and maintain high activity in eggs arrested at metaphase II. In this study, we examined the effects of BMI-1026 on GVBD and MII arrest in mouse oocytes. BMI-1026 inhibited GVBD of immature oocytes and activated MII-arrested oocytes in a concentration-dependent manner, with more than 90% of oocytes exhibiting GVBD inhibition and MII activation at 100 nM This is approximately 500$\sim$1,000 times more potent than the activity reported for the cdk inhibitors roscovitine (${\sim}50{\mu}M$) and butyrolactone (${\sim}100{\mu}M$). Based on the results of previous in vitro kinase assays, we expected BMI-1026 to inhibit only cdk1 activation in oocytes and eggs, not MAP kinase. However, in our cell-based system, it inhibited the activity of both kinases. We also found that the effect of BMI-1026 is reversible. Our results suggest that BMI-1026 inhibits GVBD and activates MII-arrested oocytes efficiently and reversibly and that it also inhibits both cdk1/histone HI kinase and MAP kinase in mouse oocytes.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.581-589
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• 1998

A regulating mechanism of the ATP-sensitive potassium channels $(K_{ATP}\;channels)$ is yet to fully explained. This study was carried out to investigate the effects of intracellular application of monocarboxylates (acetate, formate, lactate, and pyruvate) on $K_{ATP}$ channels in isolated rabbit ventricular myocytes. Single channel currents of $K_{ATP}$ channels were recorded using the excised inside-out or permeabilized attached (open-cell) patch-clamp technique at room temperature. Intracellular application of acetate, formate and pyruvate led to an inhibition of channel activity, whereas intracellular application of lactate increased channel activity. These effects were reversible upon washout. Analysis of single channel kinetics showed that monocarboxylates did not affect open-time constant and close-time constant. These results suggest that monocarboxylates participate in modulating $K_{ATP}$ channels activity in cardiac cells and that modulation of $K_{ATP}$ channels activity may resolve the discrepancy between the low $K_i$ in excised membrane patches and high levels of intracellular ATP concentration during myocardial ischemia or hypoxia.

• Archives of Pharmacal Research
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• v.17 no.4
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• pp.218-222
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• 1994

The natural product, spirostanol glycoside dioscin, was shown to directly inactivate human pleural fluid phospholipase $A_2{\;}(PLA_2)$ Inactivation was dose, and time dependent. The $IC_{50}$ was estimated at 18 .mu.M and virtually complete inactivation of the enzyme occurred at 50 .mu.M. Using Michaelis-Menten kinetics, dioscin inactivated the enzyme by a competitive inhibitory manner, the apparent Ki value was $6.9{\times}10_{-4}$. Reversibility was studied directly by dialysis method, the inhibition was reversible. Additioin of excess $Ca^{2+}$ concentration up to 8 mM did not antagonize the inhibitory activity of dioscin. Inactivation of several kinds of $PLA_2$ by dioscin is due to interaction with the active site of $PLA_2$ and may be a useful adjunt in the theraphy of inflammatory diseases.