• Archives of Pharmacal Research
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• v.22 no.2
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• pp.202-207
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• 1999

New series of catechol ether type derivatives 5, 6 have been synthesized and applied to biological tests. Even though it is ap preliminary data, some of our target molecules show the promising result against PDE IV inhibition. SAR and biological studies with studies with synthetic compounds will be discussed in detail.

• Proceedings of the PSK Conference
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• 2002.10a
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• pp.348.1-348.1
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• 2002

We synthesized various catechol ether type derivatives substituted by the hydrazine moiety and evaluated for their ability to inhibit PDE Ⅳ (Phosphodiesterase Ⅳ). These new compounds were synthesized from 4-methoxy-3-hydroxy benzaldehyde through 5 or 7 steps. Some of them have similar or more potent inhibitory activity against PDE Ⅳ than known PDE Ⅳ inhibitor. Ariflo (SB 207499). Structure activity relationship (SAR) and biological studies of described compounds will be discussed in detail. (omitted)

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.6
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• pp.731-739
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• 1997

The aim of present study is to investigate the effects of cGMP on hyperpolarization activated inward current ($I_f$), pacemaker current of the heart, in rabbit sino-atrial node cells using the whole-cell patch clamp technique. When sodium nitroprusside (SNP, $80{\mu}M$), which is known to activate guanylyl cyclase, was added, $I_f$ amplitude was increased and its activation was accelerated. However, when $I_f$ was prestimulated by isopreterenol (ISO, $1{\mu}M$), SNP reversed the effect of ISO. In the absence of ISO, SNP shifted activation curve rightward. On the contrary in the presence of ISO, SNP shifted activation curve in opposite direction. $8Br-cGMP(100\;{\mu}M)$, more potent PKG activator and worse PDE activator than cGMP, also increased basal $I_f$ but did not reverse stimulatory effect of ISO. It was probable that PKG activation seemed to be involved in SNP-induced basal $I_f$ increase. The fact that SNP inhibited ISO-stimulated $I_f$ suggested cGMP antagonize cAMP action via the activation of PDE. This possibility was supported by experiment using 3-isobutyl-1-methylxanthine (IBMX), non-specific PDE inhibitor. SNP did not affect $I_f$ when $I_f$ was stimulated by $20{\mu}M$ IBMX. Therefore, cGMP reversed the stimulatory effect of cAMP via cAMP breakdown by activating cGMP-stimulated PDE. These results suggest that PKG and PDE are involved in the modulation of $I_f$ by cGMP: PKG may facilitate $I_f$ and cGMP-stimulated PDE can counteract the stimulatory action of cAMP.

• Korean Journal of Veterinary Research
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• v.40 no.3
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• pp.479-487
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• 2000

Several recent studies demonstrate that receptor-mediated cAMP (adenosine 3',5'-monophosphate) production evokes marked change in magnesium ($Mg^{2+}$) homeostasis. The effects of dimaprit or/and phosphodiesterase (PDE) inhibitors on the $Mg^{2+}$ release from perfused guinea pig heart and collagenase-dispersed myocytes was studied to clarify an association of $H_2-histaminergic$ receptor-mediated $Mg^{2+}$ regulation with intracellular cAMP-degradation system. $Mg^{2+}$ efflux was stimulated in perfused hearts and myocytes by IBMX (3-isobutyl-1-methylxanthine), a calmodulin-sensitive PDE inhibitor, but not by RO 20-1724(4-(3-butoxy-4-methoxybenzyl)-2-imidazolidinone) or papaverine, cAMP-specific PDE inhibitors. $Mg^{2+}$ efflux was also be induced by dimaprit, a H-2-agonist. $Mg^{2+}$ effluxes induced by dimaprit were augmented by the presence of the PDE inhibitors. The augmentation of dimaprit-induced $Mg^{2+}$ effluxes by the PDE inhibitors were inhibited by ranitidine, a $H_2-antagonist$, and imipramine, a $Na^{+}-Mg^{2+}$ exchange inhibitor, in perfused hearts and myocytes and were also inhibited by amiloride in perfused hearts. These results suggest that the $H_2$-stimulated $Mg^{2+}$ effluxes from guinea pig heart can be regulated by the cytosolic nonspecific-dependent PDE systems and that it is induced by the $Na^{+}-Mg^{2+}$ exchanger stimulation.

• Journal of Microbiology and Biotechnology
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• v.27 no.2
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• pp.372-379
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• 2017

The transport of lysosomal enzymes into the lysosomes depends on the phosphorylation of their chains and the binding of the phosphorylated residues to mannose-6-phosphate receptors. The efficiency of separation depends more on the phosphodiesterases (PDEs) than on the activity of the phosphorylation of mannose residues and can be determined in vitro. PDEs play important roles in regulation of the activation of lysosomes. The expression of proteins was confirmed by western blotting. All PDE4 series protein expression was reduced in high concentrations of rolipram. As a result of observing the fluorescence intensity after rolipram treatment, the lysosomal enzyme was activated at low concentrations and suppressed at high concentrations. High concentrations of rolipram recovered the original function. Antimicrobial activity was not shown in either 10 or $100{\mu}M$ concentrations of rolipram in treated HeLa cells in vitro. However, the higher anticancer activity at lower rolipram concentration was shown in lysosomal enzyme treated with $10{\mu}M$ of rolipram. The anticancer activity was confirmed through cathepsin B and D assay. Tranfection allowed examination of the relationship between PDE4 and lysosomal activity in more detail. Protein expression was confirmed to be reduced. Fluorescence intensity showed decreased activity of lysosomes and ROS in cells transfected with the antisense sequences of PDE4 A, B, C, and D. PDE4A showed anticancer activity, whereas lysosome from cells transfected with the antisense sequences of PDE4 B, C, and D had decreased anticancer activity. These results showed the PDE4 A, B, C, and D are conjunctly related with lysosomal activity.

• Journal of Life Science
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• v.26 no.12
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• pp.1355-1359
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• 2016

Human bone marrow mesenchymal stem cells (hBM-MSCs) can differentiate into various cell types including osteoblasts, adipocytes, chondrocytes, and myocytes. Previous studies, including our own, have shown that MSCs can also differentiate into neuron-like cells. However, their rate of neuronal differentiation is not sufficient for application to stem cell therapy, which requires well-defined cell types. For this purpose, we first examined the expression of neuronal lineage markers (GFAP, MAP-2, KCNH1, Nestin, NF-M, and Tuj-1) by real-time PCR, western blot, and immunocytochemical staining. The expressions of the astrocyte marker GFAP and neuronal markers NF-M and Tuj-1 increased in neuronal differentiated MSCs (dMSCs). To improve the neuronal differentiation efficiency, PDE4, an important signaling intermediator in the progression of neuronal differentiation, was modulated using well-known inhibitors such as rolipram or resveratrol and then differentiated into neuronal cells (Roli- or RSV-dMSCs). The expressions of NF-M, Tuj-1 were increased while that of GFAP decreased in Roli- and RSV-dMSCs, which were examined by real-time PCR, western blot, and immunocytochemical staining. From these experiments, we have found that the neuronal differentiation efficiency can be ameliorated by the modulation of PDE4 activity.

• Proceedings of the Korean Institute of Communication Sciences Conference
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• 2006.07a
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• pp.394-394
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• 2006

• 제어로봇시스템학회:학술대회논문집
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• 2001.10a
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• pp.50.4-50
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• 2001

In this paper, exploiting repetitive properties, a constrained digital regulation technique for first order hyperbolic PDE systems is proposed that guarantees the stability and performance of the closed loop system.

• Proceedings of the Korean Biophysical Society Conference
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• 2002.06b
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• pp.15-15
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• 2002

Cyclic nucleotide phosphodiesterases (PDEs) regulate physiological processes by degrading ubiquitous intracellular second messengers, cAMP or cGMP. The first crystal structure of PDE4D catalytic domain and a bound inhibitor, zardaverine, was determined. Zardaverine binds to a highly conserved pocket that includes the catalytic metal binding site.(omitted)

• Journal of the Korean Vacuum Society
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• v.15 no.2
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• pp.145-151
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• 2006

The molecular assembly of p-iodo-phenyl octadecyl ether (I-POE), p-iodo-phenyl docosyl ether (I-PDE) and a binary mixture of these two molecules on graphite has been studied using a scanning tunneling microscope. Each molecular system self-assembles on the graphite surface to form a stable monolayer with a head-to-tail configuration. For the binary system, the I-POE and I-PDE molecules do not mix on the surface, preferring instead to form isolated monolayer domains. Here, the I-POE molecules are preferentially adsorbed on the graphite surface, due to the effects of alkyl chain length and the functional group on the monolayer structure.