• Toxicological Research
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• v.16 no.4
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• pp.311-315
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• 2000

Previous studies showed that benzoquinone derivatives inhibited platelet aggregation. but there is no information available on their cytotoxicity to platelets. 1n the present study. washed platelets isolated from rats were treated with 1.4-benzoquinone. a representative benzoquinone derivative. to examine its antiaggregating effect and cytotoxicity. 1.4-Benzoquinone significantly inhibited thrombin-induced platelet aggregation. Consistent with this finding. 1.4-benzoquinone suppressed cytosolic calcium increase induced by thrombin. To examine the cytotoxicity by 1 A-benzoquinone in platelets. turbidometry and lactate dehydrogenase release were measured. Treatment with 1.4-benzoquinone resulted in slight cytotoxicity (30% release at 60 min) to platelets. However. the cytotoxicity was not correlated with increase of cytosolic calcium levels in platelets. All these data suggested that 1.4-benzoquinone inhibited thrombin-induced platelet aggregation mediated by inhibition elf calcium level increase and that 1.4-benzoquinone reveals cytotoxicity to some extent without alteration of calcium level in platelets.

• Biomedical Science Letters
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• v.24 no.3
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• pp.253-262
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• 2018

Platelets are activated at sites of vascular injury via several molecules, such as adenosine diphosphate, collagen and thrombin. Full platelet aggregation is absolutely essential for normal hemostasis. Moreover, this physiological event can trigger circulatory disorders, such as thrombosis, atherosclerosis, and cardiovascular disease. Therefore, platelet function inhibition is a promising approach in preventing platelet-mediated circulatory disease. Many studies reported the involvement of mitogen-activated protein kinases (MAPKs) signaling pathways in platelet functions. However, these studies were limited. Thus, we examined MAPK signaling pathways in human platelets using specific MAPK inhibitors, such as PD98059, SB203580, and SP600125. We observed that these inhibitors were involved in calcium mobilization and influx in human platelets. They also suppressed thrombin-induced ${\alpha}$- and ${\delta}$-granule release. These results suggest that PD98059, SB203580, and SP600125 exhibit $Ca^{2+}$ antagonistic effects.

• Proceedings of the PSK Conference
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• 2003.10b
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• pp.128.2-129
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• 2003

We previously reported that phospholipase$A_2$ ($PLA_2$)-related pathway and capacitative calcium entry (CCE) via store-operated calcium channel (SOC) were involved in the regulation of muscarinic receptor- mediated sAPP release. We also observed that stimulation of muscarinic receptor associated with the inositol phosphate cascade resulted not only in increase of CCE but also in activation of PLA$_2$ in SH-SY5Y cells. In this study, we further investigated whether the $PLA_2$ isoforms differently regulate the muscarinic receptor-mediated sAPP release, and examined the relationships between activation of $PLA_2$ isoforms and CCE mediated by muscarinic receptors in SH-SY5Y cells. (omitted)

• The Korean Journal of Pharmacology
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• v.17 no.1 s.28
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• pp.1-8
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• 1981

The $Na^+$-induced calcium release and the effect of sodium on the transmitochondrial calcium flux were observed in mitochondria isolated from pig ventricular myocardium by Milipore filtration technique using radioisotope $^{45}Ca$. The release of calcium from cardiac mitochondria was induced by small amount of sodium, and was promoted by increasing sodium concentration in the incubation medium. The extent of the $Na^+$-induced calcium release was much greater in the absence of extramitochondrial calcium than in the presence of calcium. At steady state of calcium binding on the mitochondrial membrane unidirectional calcium influx was inhibited by sodium and unidirectional calcium efflux was increased., From the above results, it was suggested that calcium might be released from cardiac mitochondria in exchange with sodium through the mediation of the postulated '$Na^+/Ca^{++}$ exchange' mechanism.

• The Korean Journal of Pharmacology
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• v.29 no.1
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• pp.9-22
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• 1993

To evaluate the protective effects of calcium antagonists, oxygen radical scavengers and excitatory amino acid (EAA) antagonist on the ischemic brain damage, we induced in vitro ischemic condition (namely, lack of oxygen and glucose) to rat hippocampal slices. And the degree of ischemic damage was determined by assaying changes in biochemical parameters such as ATP content and lactate ralease, MDA production in the presence or absence of the various drugs. During experimental ischemia for up to 60 min, ATP content was decreased and the amount of lactate release was markedly increased time-dependently. By changing the reaction medium which contained oxygen and glucose those biochemical parameters were recovered. But the recovery was not complete in this experimental condition. In the same ischemic conditions verapamil and vitamine E prevented the decrease of ATP content and the increase of lactate release from the slices. And verapamil and diltiazem decreased MDA release to the reaction medium. Superoxide dismutase (SOD) and MK-801 (as EAA receptor antagonist) protected the decrease of ATP content and reduced MDA release in 20 min ischemic condition, but glutathione affected ATP content and lactate release at the same condition. When oxygen and glucose were resupplied for 20 min after ischemic condition, verapamil showed the protective effect on the changes of ATP content and lactate release, and vitamine E decreased lactate release (at 20 min ischemia) and MDA release (at 60 min ischemia). These results showed that calcium antagonist and vitamine E protect the ischemic biochemical changes from rat hippocampal slices and calcium antagonist is more potent than vitamine E to protect the ischemical brain damege.

• YAKHAK HOEJI
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• v.31 no.3
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• pp.140-148
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• 1987

The effects of orally administered ginseng ethanol extract on the calcium release from sarcoplasmic reticulum (SR) calcium pool and on the calcium content in the rat heart perfused with the Langendorff apparatus. The total amount of calcium released from SR calcium pool and the total calcium content in the rat heart were significantly decreased by 43% and 26%, respectively compared with the control.

• Journal of Microbiology and Biotechnology
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• v.22 no.5
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• pp.622-627
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• 2012

Mast cells and basophils are important effector cells in immunoglobulin-E (IgE)-mediated allergic reactions. Using the human basophilic KU812F cells, we assessed the inhibitory effects of 6-methoxyluteolin, isolated from Chrysanthemum zawadskii, in the $Fc{\varepsilon}RI$-mediated allergic reaction. We determined that 6-methoxyluteolin inhibited anti-$Fc{\varepsilon}RI$ ${\alpha}$ chain antibody (CRA-1)-induced histamine release, as well as elevation of intracellular calcium concentration $[Ca^{2+}]_i$ in a dose-dependent manner. Moreover, the inhibitory effects of 6-methoxyluteolin on the cell surface expression and the mRNA level of the $Fc{\varepsilon}RI$ ${\alpha}$ chain were determined by flow cytometric analysis and reverse transcription-polymerase chain reaction (RT-PCR), respectively. Therefore, these results show that 6-methoxyluteolin is a potent inhibitor of histamine release and calcium influx via down-regulation of the $Fc{\varepsilon}RI$ ${\alpha}$ chain.

• The Korean Journal of Physiology
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• v.27 no.1
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• pp.51-55
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• 1993

The effects of a calcium channel blocker and an activator on the release of atrial natriuretic peptide (ANP) were investigated in rats. They were volume expanded (VE) up to 5% of the body weight over 30min by being infused with iso-oncotic saline. Following VE, plasma ANP concentration markedly increased in association with increases in the right atrial pressure. Addition of either nifedipine ($0.4{\mu}m/min$) or Bay K 8644 ($0.4{\mu}m/min$) in the infusate potentiated the VE-induced release, although neither of them affected the right atrial pressure. The nifedipine added group showed a lower mean arterial pressure than the Bay K added group throughout the infusion period. VE decreased plasma renin concentration, the magnitude of which was attenuated by nifedipine but not by Bay K. It may be hypothesized that a decrease in cytoplasmic calcium is primary stimulus far the ANP release, and an increase plays o role in secondary liberation of the ANP accumulated in the interstitium into the lumen of the atria through myocardial contraction. further studies will be needed to confirm the hypothesis.

• The Korean Journal of Pharmacology
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• v.31 no.2
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• pp.207-217
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• 1995

To investigate the functional and immunological properties of the Ca-release channel in the sarcoplasmic reticulum(SR) of the eel skeletal muscle, $[^3H]ryanodine$ binding, SDS gel electrophoresis, $^{45}Ca\;release$ studies, and immunoblot assay were carried out in the SR of the eel skeletal muscle. Maximal binding sites(Bmax) and $K_D$ values of $[^3H]ryanodine$ for Ca-release channel of the SR of the eel skeletal muscle were $19.44{\pm}1.40\;pmole/mg$ protein and $15.55{\pm}1.69\;nM$, respectively. $[^3H]Ryanodine$ binding to RyR was increased by calcium and AMP. The SR of the eel skeletal muscle has two high molecular weight bands on the SDS PAGE. The mobility of upper band was more slower than the single band of the rabbit skeletal muscle, and that of the lower band was similar with the single band of canine cardiac muscle. Vesicular $^{45}Ca-release$ was activated by calcium. Ca-induced $^{45}Ca-release$ was significantly inhibited by $MgCl_2(2\;mM)$, ruthenium red$(10\;{/mu}M)$ or tetracaine(1 mM), but not by high concentration of calcium itself. AMP-induced $^{45}Ca-release$ was slightly occurred only in the absence of calcium, it was not inhibited by $MgCl_2$ or ruthenium red. Caffeine also increased $^{45}Ca-release$ from the SR vesicles, but it was not affected by $MgCl_2$ or ruthenium red. Polyclonal Ab against rat skeletal muscle RyR is reacted with that of rabbit, but not reacted with that of the eel skeletal muscle. These results suggested that ryanodine receptor of the SR of the eel skeletal muscle is showing some similar properties with that of mammalian skeletal muscle, but might be an another isotype channel having two bands which is less sensitive to AMP, not cross-reacted with antisera against rat RyR, and not inhibited by high concentration of calcium.

• Development and Reproduction
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• v.7 no.2
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• pp.95-103
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• 2003

Intracellular calcium is an important physiological factor in most cells, and ruthenium red and ryanodine play an important role as calcium modulators. Ruthenium red inhibits calcium-induced calcium release(CICR) from the intracellular calcium store. Ryanodine activates calcium release through ryanodine channel. The present experiment was performed to investigate the effects of two modulators on calcium ion metabolism and to determine their dose-dependency in oocyte and early embryo of mouse. Intracellular calcium ion concentration was measured in realtime by using confocal laser scanning microscope(CLSM) after loading of Fluo-3/AM in mouse oocytes and early embryos. Ruthenium red decreased intracellular calcium ion concentration in oocytes and early embryos at its high concentration(30, 300 $\mu$M). Ryanodine increased intracellular calcium ion concentration in oocytes and early embryos in low concentration(0.01 $\mu$M) but decreased that at higher concentrations(1, 10 $\mu$M). These results indicate that two modulators affected calcium ion metabolism in oocyte and early embryo of mouse, and their dose-dependency was different from somatic cell including myocytes.