• The Korean Journal of Physiology and Pharmacology
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• v.9 no.1
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• pp.45-53
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• 2005

The present study was designed to examine the effect of d-amphetamine on CA release from the isolated perfused model of the rat adrenal gland, and to establish its mechanism of action. Damphetamine $(10{\sim}100{\mu}M$), when perfused into an adrenal vein of the rat adrenal gland for 60 min, enhanced the CA secretory responses evoked by ACh ($5.32{\times}10^{-3}$ M), excess $K^+$ ($5.6{\times}10^{-2}$ M, a membrane depolarizer), DMPP ($10^{-4}$ M, a selective neuronal nicotinic $N_n-receptor$ agonist) and McN-A-343 ($10^{-4}$ M, a selective $M_1-muscarinic$ agonist) only for the first period (4 min), although it alone has weak effect on CA secretion. Moreover, d-amphetamine ($30{\mu}M$) in to an adrenal vein for 60 min also augmented the CA release evoked by BAY-K-8644, an activator of the dihydropyridine L-type $Ca^{2+}$ channels, and cyclopiazonic acid, an inhibitor of cytoplasmic $Ca^{2+}$ ATPase only for the first period (4 min). However, in the presence of high concentration ($500{\mu}M$), d-amphetamine rather inhibited the CA secretory responses evoked by the above all of secretagogues. Collectively, these experimental results suggest that d-amphetamine at low concentrations enhances the CA secretion from the rat adrenal medulla evoked by cholinergic stimulation (both nicotininc and muscarinic receptors) as well as by membrane depolarization, but at high concentration it rather inhibits them. It seems that d-amphetamine has dual effects as both agonist and antagonist at nicotinic receptors of the isolated perfused rat adrenal medulla, which might be dependent on the concentration. It is also thought that these actions of d-amphetamine are probably relevant to the $Ca^{2+}$ mobilization through the dihydropyridine L-type $Ca^{2+}$ cha$N_n$els located on the rat adrenomedullary chromaffin cell membrane and the release of $Ca^{2+}$ from the cytoplasmic store.

• Journal of Ginseng Research
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• v.35 no.1
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• pp.92-103
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• 2011

Ginseng has been used as a general tonic agent to invigorate human body. In the present study, we isolated novel glycolipoproteins from ginseng that activate $Ca^{2+}$-activated $Cl^-$ channel (CaCC) in Xenopus oocytes and transiently increase intracellular free $Ca^{2+}$ concentration ($[Ca^{2+}]_i$) in mouse Ehrlich ascites tumor cells. We named the active ingredients as gintonin. Gintonin exists in at least six different forms. The native molecular weight of gintonin is about 67 kDa but its apparent molecular weight is about 13 kDa, indicating that gintonin might be a pentamer. Gintonin is rich in hydrophobic amino acids. Its main carbohydrates are glucose and glucosamine. Its lipid components are linoleic, palmitic, oleic, and stearic acids. Gintonin actions were blocked by U73122, a phospholipase C inhibitor, 2-aminoethxydiphenyl borate, an inositol 1,4,5-trisphosphate receptor antagonist, or bis (o-aminophenoxy) ethane-N,N,N0,N0-tetracetic acid acetoxymethyl ester, a membrane permeable $Ca^{2+}$ chelator. In the present study, we for the first time isolated novel gintonin and showed the signaling pathways on gintonin-mediated CaCC activations and transient increase of $[Ca^{2+}]_i$. Since $[Ca^{2+}]_i$ as a second messenger plays a pivotal role in the regulation of diverse $Ca^{2+}$-dependent intracellular signal pathways, gintonin-mediated regulations of $[Ca^{2+}]_i$ might contribute to biological actions of ginseng.

• The Korean Journal of Ecology
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• v.16 no.2
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• pp.169-180
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• 1993

Soils of four combinations, sand with high content of organic matter(SL), sand with low content of OM(SS), siltyl loam with high content of OM(LL) and silty loam with low content OM (LS), were filled on column and then percolated with simulated sulfuric acid rain with pH 5.6, 4.0, 3.5, 3.0 and 2.5. From soil leachates, pH and concentrations of basic cations and Al were determined. Cation concentrations in the leachates increased as pH of the rain decreased. The orders of buffering capacity of soil, leachability of cation from soil, leaching sensitivity of ion andbase saturation sensitivity of soil to acidity of the rain water were SS$\leq$K <$\leq$LL

• Korean Journal of Pharmacognosy
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• v.36 no.1 s.140
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• pp.17-20
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• 2005

We previously reported that the exogenous administration of cumambrin A, a sesquiterpene lactone from the dried flowers of Chrysanthemum boreale Makino has a pharmacological effect on normalization of blood pressure in the spontaneously hypertensive rats (SHR). In the present study, we further investigated the effect of cumambrin A on the relaxation of phenylephrine-induced precontracted rat aortic artery rings. The potency of cumambrin A was than compared to verapamil, a well known $Ca^{2+}-channel$ blocker. The results demonstrate that the isolated rat aortic arteries are relaxed to basal tension at a concentration of $5{\times}10^{-5}\;M$ cumambrin A treatment. The results also show that the phenylephrine-induced contraction is inhibited by a pretreatment of cumambrin A. Co-treatment of cumambrin A and verapamil showed a strong synergetic effect on the relaxation of rat aortic artery rings. Thus, these data demonstrate that cumambrin A is a potent relaxant of rat aortic smooth muscle and suggest that cumambrin A modulates intracellular or extracellular $Ca^{2+}$ mobilization.

• Journal of Applied Biological Chemistry
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• v.62 no.4
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• pp.425-431
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• 2019

Platelet activation is essential for hemostatic process on blood vessel damage. However, excessive platelet activation can cause some cardiovascular diseases including atherosclerosis, thrombosis, and myocardial infarction. Scoparone is commonly encountered in the roots of genus Artemisia or Scopolia, and has been studied for its potential pharmacological properties including immunosuppression and vasorelaxation, but antiplatelet effects of scoparone have not been reported yet. We investigated the effect of scoparone on human platelet activation prompted by an analogue of thromboxane A₂, U46619. As the results, scoparone dose-dependently increased cyclic adenosine monophosphate (cAMP) levels as well as cyclic guanosine monophosphate (cGMP) levels, both being aggregation-inhibiting molecules. In addition, scoparone strongly phosphorylated inositol 1, 4, 5-triphosphate receptor (IP3R) and vasodilator-stimulated phosphoprotein (VASP), substrates of cAMP dependent kinase and cGMP dependent kinase. Phosphorylation of IP₃R by scoparone resulted in inhibition of Ca²⁺ mobilization in calcium channels in a dense tubular system, and phosphorylation of VASP by scoparone led to an inability of fibrinogen being able to bind to αIIb/β3. Finally, scoparone inhibited thrombin-induced fibrin clotting, thereby reducing thrombus formation. Therefore, we suggest that scoparone has a strong antiplatelet effect and is highly probable to prevent platelet-derived vascular disease.

• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.91-102
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• 1992

In $Ca^{++}$ containing media, arachidonic acid markedly stimulated superoxide and $H_2O_2$ generation and activated NADPH oxidase. In $Ca^{++}$ free media, stimulatory action of arachidonic acid on NADPH oxidase was not detected. Arachidonic acid-stimulated respiratory burst was inhibited by EGTA, TMB-8, verapamil, diltiazem, nifedipine, dibucaine, lidocaine, CCCP, 2,4-dinitrophenol, sodium arsenate, chlorpromazine, theophylline, $HgCl_2$, PCMB and PCMBSA but not affected by tetrodotoxin, tetraethylammonium chloride and procaine. EGTA almost completely inhibited release of ${\beta}-glucuronidase$ by arachidonic acid and verapamil, CCCP and theophylline slightly inhibited it, whereas dibucaine did not show any significant effect. Arachidonic acid induced $Ca^{++}$ release from intact neutrophils and it was decreased by TMB-8. Arachidonic acid-induced elevation of intracellular free $Ca^{++}$ level was inhibited by EGTA and CCCP and slightly inhibited by TMB-8. Amount of intracellular free $Ca^{++}$ increased by either arachidonic acid plus verapamil or arachidonic acid plus dibucaine was greater than that by arachidonic acid alone. These results suggest that various changes of biochemical events may be implicated in the functional expression in neutrophils activated by arachidonic acid. Arachidonic acid appears to elevate cytosolic free $Ca^{++}$ level by stimulating $Ca^{++}$ release from intracellular $Ca^{++}$ storage sites. During activation of neutrophils, $Ca^{++}$ influx and efflux may be accomplished, simultaneously.

• International Journal of Oral Biology
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• v.31 no.4
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• pp.127-133
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• 2006

[ $H_2O_2$ ], a member of reactive oxygen species (ROS), is known to be involved in the mediation of physiological functions in a variety of cell types. However, little has been known about the physiological role of $H_2O_2$ in exocrine cells. Therefore, in the present study, the effect of $H_2O_2$ on cholecystokinin (CCK)-evoked $Ca^{2+}$ mobilization and amylase release was investigated in rat pancreatic acinar cells. Stimulation of the acinar cells with sulfated octapeptide form of CCK (CCK-8S) induced biphasic increase in amylase release. Addition of $30\;{\mu}M\;H_2O_2$ enhanced amylase release caused by 10 pM CCK-8S, but inhibited the amylase release induced by CCK-8S at concentrations higher than 100 pM. An ROS scavenger, $10\;{\mu}M$ Mn(III)tetrakis(4-benzoic acid)porphyrin chloride, increased amylase release caused by CCK-8S at concentrations higher than 100 pM, although lower concentrations of CCK-8S-induced amylase release was not affected. To examine whether the effect of $H_2O_2$ on CCK-8S-induced amylase release was exerted via modulation of intracellular $Ca^{2+}$ signaling, we measured the changes in intracellular $Ca^{2+}$ concentration $([Ca^{2+}]_i)$ in fura-2 loaded acinar cells. Although $30\;{\mu}M\;H_2O_2$ did not induce any increase in $[Ca^{2+}]_i$ by itself, it increased the frequency and amplitude of $[Ca^{2+}]_i$ oscillations caused by 10 pM CCK-8S. However, $30\;{\mu}M\;H_2O_2$ had little effect on 1 nM CCK-8S-induced increase in $[Ca^{2+}]_i$. ROS scavenger, 1 mM N-acetylcysteine, did not affect $[Ca^{2+}]_i$ changes induced by 10 pM or 1 nM CCK-8S. Therefore, it was concluded that $30\;{\mu}M\;H_2O_2$ enhanced low concentration of CCK-8S-induced amylase release probably by increasing $[Ca^{2+}]_i$ oscillations while it inhibited high concentration of CCK-8S-induced amylase release.

• The Korean Journal of Physiology
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• v.24 no.2
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• pp.293-303
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• 1990

The contractile action of barium $(Ba^{2+})$ was investigated in the arterial strip of rabbit renal artery. The helical strip of isolated renal artery was immersed in the Tris-buffered Tyrode's solution equilibrated with 100% $O_2$ at $37^{\circ}C$ and its isometric tension was measured. $Ba^{2+}-induced$ contraction of arterial strip was dose-dependent and its maximal tension corresponded to $92.1{\pm}4.5%$ of tension by $K^+(100\;mM)$. $Ba^{2+}-induced$ contraction did not show the tachyphylactic phenomenon in the normal Tyrode's solution. $Ba^{2+}$ induced the tonic contraction in the $Ca^{2+}-free$ tyrode's solution and that was increased by the extracellula addition of $Ca^{2+}$. During the repeated exposure of the same dose of $Ba^{2+}\;(10\;mM)$ in the $Ca^{2+}-free$ Tyrode's solution, $Ba^{2+}-induced$ contraction was progressively decreased. Even though the intracellular NE-and caffeine-sensitive $Ca^{2+}$ was depleted, $Ba^{2+}$ induced the tonic contraction. After the pretreatment of lanthnum or verapamil, $Ba^{2+}$ did not induce contraction. $Ba^{2+}-induced$contraction was suppressed by extracellular $K^+$ in the normal Tyrode's solution and that was dependent on $K^+$ concentration. Suppressive effect of $K^+\;(14\;mM)$ on the $Ba^{2+}-induced$ contraction was also dependent on the intracellular $Ca^{2+}$ concentration. From the above resuts, it is suggested that $Ba^{2+}$ activate indirectly the contractile process by promoting the mobilization of intracellular $Ca^{2+}$ and the influx of extracellular $Ca^{2+}$. It is also suggested that action of $Ba^{2+}$ on the $Ca^{2+}-activated$ $K^+$ channel can result in the depolarization of cell membrane in the rabbit renal artery.

• Journal of Applied Biological Chemistry
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• v.63 no.4
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• pp.339-345
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• 2020

Euchrestaflavanone A (EFA) is a flavonoid found in the root bark of Cudrania tricuspidata. C. tricuspidata extract, widely used throughout Asia in traditional medicine, has been investigated phytochemically and biologically and is known to have anti-obesity, anti-inflammatory, and anti-tumor effects. It has been reported that C. tricuspidata extract also possesses anti-platelet effects; however, the mechanism of its anti-platelet and anti-thrombotic activities is yet to be elucidated. In this study, we investigated the effects of EFA on the modulation of platelet function using collagen-induced human platelets. Our results showed that EFA markedly inhibited platelet aggregation. Furthermore, it downregulated glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production, and clot retraction, but upregulated the cyclic adenosine monophosphate-dependent pathway. Taken together, EFA possesses strong anti-platelet and anti-thrombotic properties and is a potential therapeutic drug candidate to prevent platelet-related thrombosis and cardiovascular disease.

• Korean Journal of Pharmacognosy
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• v.51 no.4
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• pp.231-237
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• 2020

Euchrestaflavanone B (EFB) is a flavonoid that can be found in root bark, particularly in Cudrania tricuspidata (C. tricuspidata). The extract of C. tricuspidata is widespread throughout Asia and used in traditional medicine. In a previous study, we found anti-platelet effects of substances isolated from C. tricuspidata on collagen-induced human platelets. However, the C. tricuspidata still contains numerous substances, thus, we have searched new candidate, EFB isolated from C. tricuspidata for anti-platelet effect. Our results showed that EFA inhibited collagen-induced platelet aggregation and glycoprotein IIb/IIIa (αIIb/β3)-mediated signaling events, including platelet adhesion, granule secretion, thromboxane A2 production and clot retraction. These results suggest that EFA has inhibitory effects on human platelet activities and thrombus formation and has potential value as a natural substance for preventing platelet-induced thrombosis.