• The Korean Journal of Physiology and Pharmacology
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• v.20 no.1
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• pp.9-14
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• 2016

Adenosine 3',5'-cyclic monophosphate (cAMP) participates in the regulation of numerous cellular functions, including the $Na^+-K^+$-ATPase (sodium pump). Ouabain, used in the treatment of several heart diseases, is known to increase cAMP levels but its effects on the atrium are not understood. The aim of the present study was to examine the effect of ouabain on the regulation of atrial cAMP production and its roles in atrial endothelin-1 (ET-1) secretion in isolated perfused beating rabbit atria. Our results showed that ouabain ($3.0{\mu}mol/L$) significantly increased atrial dynamics and cAMP levels during recovery period. The ouabain-increased atrial dynamics was blocked by KB-R7943 ($3.0{\mu}mol/L$), an inhibitor for reverse mode of $Na^+-Ca^{2+}$ exchangers (NCX), but did not by L-type $Ca^{2+}$ channel blocker nifedipine ($1.0{\mu}mol/L$) or protein kinase A (PKA) selective inhibitor H-89 ($3.0{\mu}mol/L$). Ouabain also enhanced atrial intracellular cAMP production in response to forskolin and theophyline ($100.0{\mu}mol/L$), an inhibitor of phosphodiesterase, potentiated the ouabain-induced increase in cAMP. Ouabain and 8-Bromo-cAMP ($0.5{\mu}mol/L$) markedly increased atrial ET-1 secretion, which was blocked by H-89 and by PD98059 ($30{\mu}mol/L$), an inhibitor of extracellular-signal-regulated kinase (ERK) without changing ouabain-induced atrial dynamics. Our results demonstrated that ouabain increases atrial cAMP levels and promotes atrial ET-1 secretion via the mitogen-activated protein kinase (MAPK)/ERK signaling pathway. These findings may explain the development of cardiac hypertrophy in response to digitalis-like compounds.

• Journal of Korean Medicine Rehabilitation
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• v.25 no.1
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• pp.27-44
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• 2015

Objectives This study was carried out to find the effects of Gami-cheongyulsaseub-tang (hereinafter referred to GCST) on the inhibition of zymosan-induced pain in rats and collagen II-induced arthritis (CIA) in DBA/1J mouse. Methods As an acute inflammatory pain model, peripheral inflammation was induced by intraplantar injection of zymosan into the right hind paw in rats and then the hyperalgesia and pain regulating factors in spinal cord were analyzed. As a chronic inflammation model, the mixture of collagen II and complete Freund's adjuvant was treated into mice to establish rheumatoid arthritis and then body weight, thickness of hind paw, pathological change of spleen, immunological rheumatoid factor (IgG1, IgG2a, IgG2b, IgM and anti-collagen II), pro-inflammatory cytokines, and bone injury were analyzed. Results In the acute inflammatory pain model, GCST significantly inhibited the thermal and mechanical hyperalgesia and the pain regulating factors, including Fos, CD11b, PKA and PKC, in the spinal cord with a dose-dependent manner. In the chronic rheumatoid arthritis model, GCST administration decreased arthritic index and paw edema as compared with CIA control group. In particular, GCST reduced significantly the serum levels of total IgG2a, IgG2b, IgM, and specific anti-collagen II, but not total IgG1. GCST also resulted in the attenuation of bone injury and spleen enlargement/adhesion in CIA mice. Moreover, the secretion of pro-inflammatory cytokines TNF-${\alpha}$ and IL-$1{\beta}$ in CIA mice was significantly reduced by GCST in a dose-dependent manner. Conclusions Comparison of the results in this study showed that GCST had anti-nociceptive and immunomodulatory effects. These data imply that GCST can be used as an effective drug for not only rheumatoid arthritic pain but also other auto-immune diseases.

• Journal of Life Science
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• v.16 no.4
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• pp.691-698
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• 2006

Phospholipase D (PLD) is known to play an important role in a variety of cells. However, little is known about $CoCl_2-mediated$ PLD signaling. In this study we demonstrated for the first time that $CoCl_2$ stimulates PLD activity and increases expression of cyclooxygenase-2 (COX-2), which is known to mediate inflammatory reaction. $CoCl_2-induced$ PLD activity was assessed by measuring the formation of $[^3H]$ phosphatidylbutanol (PtdBut), the product of PLD-mediated transphosphatidylation, in the presence of 1-butanol. To study mechanism of PLD signaling induced by $CoCl_2$, U87 human glioblastoma cells were stimulated by $CoCl_2$ and regulators of PLD activity induced by $CoCl_2$ were investigated using several inhibitors of signaling proteins. Moreover, PLD activation by $CoCl_2$ increased not only expression of COX-2 protein but also COX-2 promoter activity. In summary, these results suggest that $CoCl_2$ increases expression of COX-2 protein via PLD in human U87 glioblastoma cells.

• Journal of Embryo Transfer
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• v.19 no.2
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• pp.89-99
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• 2004

Stretch-activated channels (SACs) responds to membrane stress with changes in open probability (Po). They play essential roles in regulation of cell volume and differentiation, vascular tone, and in hormonal secretion. SACs highly present in Xenopus oocytes and Ascidian oocytes are suggested to be involved in the regulation of pH and fluid transport to balance the osmotic pressure, but remain unclear in mammanlian oocytes. This study was investigated to find the presence of SACs in hamster oocytes and to examine their electrophysiological properties. To infer a role of SAC in relation to the development of early stage, we followed up to the stage of two-cell zygote with patch clamp techniques. Single channels were elicited by negative pressure (lower than ­15 cm$H_2O$). Interestingly, SACs were dependent on permeable cations such as $Na^+$ or $K^+$. As permeable cation removed from both sides across the membrane, SAC activity completely disappeared. When permeable cations present only in intracellular compartment, outward currents appeared at positive potentials. In contrast to this, inward currents occurred only at the negative voltage when permeable cation absent in cell interior. These result suggests that SAC carry cations through the nonselective cation channel (NSC channel). Taken together, we found that stretch activated channels present in hamster oocyte and the channel may carry cations through NSC channels. This stretch activated-NSC channels may play physiological role(s) in oocyte growth, maturation, fertilization and embryogenesis in fertilized oocytes to two-cell zygotes of hamster.

• The Korean Journal of Pesticide Science
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• v.2 no.1
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• pp.46-52
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• 1998

The hydrolysis rate of insecticidal buprofezin(IUPAC : tert-butylimino-3-isopropyl-5-phenylperhydro-1,3,5-thiadiazin-4-one) in the range of pH 2.0 and 12.0 have been examined in 15%(v/v) aqueous dioxane at $45^{\circ}C$. The hydrolysis mechanism of buprofezin is proposed from the pH-effect, solvent effect(${\ell}{\gg}m$), thermodynamic parameter(${\Delta}H^{\neq}$=11.12 $Kcal{\cdot}mol^{-1}$ &, ${\Delta}S^{\neq}=5.0e.u.$), rate equation and hydrolysis product, l-isopropyl-3-phenyl urea. General acid catalyzed hydrolysis and specific acid catalyzed($k_{H3O+}$) hydrolysis through $A-S_{E}2$ and A-2(or $A_{AC}2$) reaction mechanism with orbital-control reaction proceed below pH 8.0 and above pH 9.0, the nucleophilic addition-elimination, $Ad_{N}-E$ mechanism via tetrahedral($sp^{3}$) intermediate is initiation by general base catalyzed($k_{H2O}$) reaction. Buprofezin was more stable in alkaline ($k=10^{-8}sec.^{-1}$) than acid solutions from the sigmoid pH-rate profile. And the half-life($t=\frac{1}{2}$) of hydrolysis reaction in neutral aqueous solution(pH 7.0) at $45^{\circ}C$ was about 3 months.

• Journal of Life Science
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• v.23 no.5
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• pp.609-615
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• 2013

Glyceollin I has gained attention as a useful therapy for various dermatological diseases. However, the binding property of glyceollin I to the mammalian adenylyl cyclase (hereafter mAC), a critical target enzyme for the down-regulation of skin melanogenesis, has not been fully explored. To clarify the action mechanism between glyceollin I and mAC, we first investigated the molecular docking property of glyceollin I to mAC and compared with that of SQ22,536, a well-known mAC inhibitor, to mAC. Glyceollin I showed superiority by forming three hydrogen bonds with Asp 1018, Trp 1020, and Asn 1025, which exist in the catalytic site of mAC. However, SQ22,536 formed only two hydrogen bonds with Asp 1018 and Asn 1025. Secondly, we confirmed that glyceollin I effectively inhibits the formation of forskolin-induced cAMP and the phosphorylation of PKA from a cell-based assay. Long term treatment with glyceollin I had little effect on the cell viability. The findings of the present study also suggest that glyceollin I may be extended to be used as an effective inhibitor of hyperpigmentation.