• BMB Reports
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• v.29 no.1
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• pp.11-16
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• 1996

The present study showed that receptor-mediated activation of rabbit kidney proximal tubule cells by angiotensin II, the $Ca^{2+}$ ionophore A23187, or the protein kinase C activator phorbol myristate acetate (PMA) all stimulated phospholipase D (PLD). This was demonstrated by the increased formation of phosphatidic acid, and in the presence of 0.5% ethanol, phosphatidylethanol (PEt) accumulation. Angiotensin II leads to a rapid increase in phosphatidic acid and diacylglycerol, and phosphatidic acid formation preceeded the formation of diacylglycerol. This result suggests that some phosphatidic acid seems to be formed directly from phosphatidylcholine hydrolyzed by Pill. On the other hand, EGTA substantially attenuated angiotensin II and A23187-induced PEt formation, and when the cells were pretreated with verapamil angiotensin II-induced Pill activation was completely abolished. These results provide the evidence that calcium ion influx is essential for the agonist-induced Pill activation. In addition, staurosporine, an inhibitor of protein kinase C, strongly inhibited PMA-induced PEt formation, but was ineffective on angiotensin II-induced PEt accumulation. $GTP{\gamma}S$ also stimulates PEt formation in digitonin-permeabilized cells, but pretreatment of the cells with pertussis toxin failed to suppress angiotensin II-induced PEt formation. From these results, we conclude that in the rabbit kidney proximal tubule cells the mechanisms of angiotensin II- and PMA-induced Pill activation are different from each other and mediated via a pertussis toxin-insensitive trimeric G protein.

• Preventive Nutrition and Food Science
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• v.21 no.4
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• pp.323-329
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• 2016

Achyranthes japonica Nakai (AJN) water extract has a variety of physiological properties, including anti-diabetic, anti-cancer, anti-inflammatory, anti-microbial, and anti-oxidative activities. In the present study, the inhibitory effects of AJN extract were investigated in high affinity immunoglobulin E receptor ($Fc{\varepsilon}RI$)-mediated KU812F cells activation. AJN extract showed suppressive effects on histamine release and intracellular calcium [$Ca^{2+}$]i elevation from anti$Fc{\varepsilon}RI$ antibody (CRA-1)-stimulated cells in a dose-dependent manner. Flow cytometric analysis showed that AJN extract treatment caused a dose-dependent decrease in the cell surface $Fc{\varepsilon}RI$ expression and the binding between the cell surface $Fc{\varepsilon}RI$ and the IgE antibody. Moreover, reverse transcription-polymerase chain reaction analysis showed that levels of the mRNA for the $Fc{\varepsilon}RI$ ${\alpha}$ chain was decreased by treatment with AJN extract. These results indicate that AJN extract may exert anti-allergic effects via the inhibition of calcium influx and histamine release, which occurs as a result from the downregulation of the binding of IgE antibody to cell surface $Fc{\varepsilon}RI$. This mechanism may occur through $Fc{\varepsilon}RI$ expression inhibition.

• Journal of Ginseng Research
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• v.31 no.3
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• pp.117-126
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• 2007

Ginseng, the root of Panax species, a well-known herbal medicine has been used as a traditional medicine for thousands of years and is now a popular and worldwide used natural medicine. Ginseng has been used primarily as a tonic to invigorate weak bodies to help the restoration of homeostasis in a wide range of pathological conditions such as cardiovascular diseases, cancer, immune deficiency and hepatotoxicity. Although conclusive clinical data in humans is still missing, recent research results have suggested that some of the active ingredients ginseng exert beneficial effects on central nervous system (CNS) disorders and neurodegenerative diseases, suggesting it could be used in treatment of psychotic disorders. Data from neural cell cultures and animal studies contribute to the understanding of these mechanisms that involve inhibitory effects on stress-induced corticosterone level increasing and modulating of neurontransmitters, reducing $Ca^{2+}$ over-influx, scavenging of free radicals and counteracting excitotoxicity. In this review, we focused on recently reported medicinal effects of ginseng and summarized the possibility of its applications on psychotic disorders.

• Journal of fish pathology
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• v.9 no.1
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• pp.53-63
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• 1996

The present study was undertaken to investigate the physiological characteristics of the cholinergic responses in the tilapia dorsal aorta. In vessels under resting tension or precontracted with norepinephrine, acetylcholine caused only concentration-dependent vasoconstrictions. Contractile response to acetylcholine was not affected by the removal of endothelium or the application of methylene blue. Atropine, gallamine or pirenzepine shifted concentration-response curve to the right. However pirenzepine showed a similar effect on the curve only at high concentration ($1{\times}10^{-5}$M). Acetylcholine-induced vasoconstriction was not markedly influenced by indomethacin, or verapamil, but was almost abolished in the calcium-free physiological buffer solution. These results suggest that acetylcholine produces only an endothelium-independent vasoconstriction in tilapia dorsal aorta and that the contractile effect of acetylcholine is mainly mediated by the activation of $M_2$ subtype receptor, which might be associated with the extracellular calcium influx through receptor-linked calcium channel.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.67-74
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• 1996

Cholecystokinin octapeptide (CCK-8), acetylcholine (ACh) and KCl caused a dose dependent contraction in muscle cells enzymatically digested from cat gallbladder. Maximal contraction was obtained at concentration of $10^{-9}M$ for CCK-8, $10^{-5}M$ for ACh and 20mM for KCl. CCK-8 induced contraction was unaffected in calcium free physiological salt solution (PSS) and was completely blocked by strontium substitution for calcium (p<0.001). In contrast, KCl evoked contraction was blocked in calcium free PSS (p<0.01) but was unaffected by strontium replacement of calcium. The contraction elicited by ACh was only slightly reduced in calcium free PSS (p<0.05) and was unaltered by strontium. Muscle cells permeabilized with saponin contracted in response to inositol 1,4.5-trisphosphate $(IP_3)$ and CCK-8. The contraction was blocked by the calmodulin antagonist CGS 9343B (p<0.001), whereas heparin completely blocked the effect of $IP_3$ (p<0.001). The protein kinase C (PKC) antagonist H7 had no effect on either agonist. We conclude that CCK-8 induced gallbladder muscle contraction is mediated by $IP_3$ dependent intracellular calcium release from intracellular stores and a calmodulin dependent pathway; ACh may utilize both extracellular and intracellular calcium. KCl causes muscle contracrion through influx of extracellular calcium and a calmodulin independent machanism.

• The Korean Journal of Pharmacology
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• v.32 no.1
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• pp.51-56
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• 1996

The objectives of this study is to find out mechanism of vasodilating effects of ANP in 2K-1C renovascular hypertensive rat aorta and to compare with those of normotensive rat aorta. In 2K-1C renovascular hypertensive rat, average arterial blood pressure and plasma renin activity were higher than in normotensive rat. In 2K-1C renovascular hypertensive rat aorta, NE sensitivity was more increased and maximal contraction of aorta by NE was higher than those of normotensive rat aorta. ANP inhibited NE-induced contraction in both 2K-1C renovascular hypertensive and normotensive rat aorta, concentration-dependently. However, ANP was less effective for relaxing NE-induced contraction in 2K-1C renovascular hypertensive rat aorta than in normotensive rat aorta. ANP inhibited $^{45}Ca^{2+}$ uptake induced by NE in both 2K-1C renovascular hypertensive and normotensive rat aorta. From these results. inhibition of $Ca^{2+}$ influx may be one of the vasodilating mechanism of ANP in 2K-1C renovascular hypertensive rat aorta. Although the potency of ANP in relaxing NE-induced contractions was attenuated, the efficacy of ANP was not changed in 2K-1C renovascular hypertensive rat aorta compared with that of ANP in normotensive rat aorta. Abbreviations: ANP, Atrial natriuretic peptide; 2K-1C, 2-kidney 1 clip; NE, norepinephrine; SHR, Spontaneously hypertensive rat; DOC, Deoxycorticosterone; EDTA, Ethylenediaminetetra-acetic acid; PSS, Physiological salt solution; TRIS, tris(hydroxymethyl) aminomethane

• Korean Journal of Veterinary Research
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• v.35 no.2
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• pp.229-236
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• 1995

The effect of ${\alpha}_1$-adrenoceptor(${\alpha}_1$-AR) stimulation on intracellular pH($pH_i$), $Na^+$ activity($a_{Na}{^i}$) and contractility were investigated in isolated papillary muscles of euthyroid or hyperthyroid guinea pig with conventional microelectrode, $Na^+$ or $H^+$-selective microelectrodes, and tension transducer. Stimulation of the ${\alpha}_1$-AR by phenylephrine produced a decrease in $a_{Na}{^i}$ in euthyroid preparations. This decrease in $a_{Na}{^i}$ was abolished in presence of PKC activator, phorbol dibutyrate, and increased contrary to decrease. Phenylephrine also increased $a_{Na}{^i}$ in hyperthyroid ones. However, phenylrephtine produced an increase in $pH_i$ in both euthyroid and hyperthyroid ones. These changes were blocked by prazosin, an antagonist of ${\alpha}_1$-AR. These findings suggest that the changes in $a_{Na}{^i}$ and $pH_i$ are mediated by a stimulation of $Na^+-H^+$ exchange via ${\alpha}_1$-AR stimulation. This study focused on the increase in $a_{Na}{^i}$, $pH_i$ and contractility. The increase in $pH_i$ was blocked by amiloride or EIPA, $Na^+-H^+$ exchange inhibitors. Therefore, the increase in $a_{Na}{^i}$ and $pH_i$ mediated by ${\alpha}_1$-AR appeared to be due to an influx of $Na^+$ and a reduction of $H^+$ through $Na^+-H^+$ exchange. This study also revealed that the increase in $pH_i$ and $a_{Na}{^i}$ might be related to the sustained positive inotropic response. The $a_{Na}{^i}$ increase may contribute to the intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchange, and the $pH_i$ increase could cause an increase in the $Ca^{2+}$ sensitivity of myofilaments and may augment the ${\alpha}_1$-AR-mediated positive inotropic response.

• The Korean Journal of Physiology
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• v.17 no.1
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• pp.45-54
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• 1983

Contractile responses of myocardium and vascular smooth muscle to angiotensin II were studied in isolated rabbit papillary muscles and aortic helical strips, with respect to the sensitivity and the mechanism of action. All experiments were performed in $HCO-_3\;-buffered Tyrode solution which was aerated with $3%\;CO_2-97%\;O_2$ and kept pH 7.35 at $35^{\circ}C$. Action potentials were measured by conventional microelectrode technique in the papillary muscles. Helical strips of vascular smooth muscle were prepared from the descending thoracic aorta of the rabbit. Angiotensin II elicited a positive inotropic effect in doses from $10^{-8}$ to $10^{-6}\;M$, and this effect was dose-dependent and characterized by a symmetrical increase of maximum dP/dt during contraction and relaxation phase. Slow responses (or slow action potentials) were induced by A. II $(10^{-6}\;M)$ in the papillary muscle hypopolarized by 27 mM $K^+$. These A. II-induced slow action potentials were eliminated by verapamil (2 mg/l), but not affected by propranolol $(10^{-5}\;M)$. In aortic helical strips, contractile force was increased dose-dependently in the range of $10^{-10}{\sim}10^{-7}\;M$ A. II. $ED_{50}$ in aorta was $3{\times}10^{-9}\;M$ A. II, whereas that in paillary muscle was $2.5{\times}10^{-7}\;M$ A. II. A. II contracted vascular smooth muscle in depolarizing concentration of $K^+$ (100 mM $K^+$), and also produced a sustained contraction even in the presence of verapamil and regitine. The results of this experiment suggest that the primarily important physiological role of A. II is the action on the blood vessel, and the positive inotropic effect of A. II in papillary muscle results from the increase of slow inward $Ca^{++}$ current, and that A. II-induced contraction of aorta is independent of transmembrane potential and associated with promoting bet transmembrane $Ca^{++}\;-influx$ and the mobilization of cellular $Ca^{++}$.

• Korean Journal of Environmental Agriculture
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• v.20 no.1
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• pp.20-27
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• 2001

Stream water chemistry in the abandoned Boeun Jeil coal mine area was studied for a period of 3 months, including rainy and dry season. The stream waters were a nearly neutral and slightly alkali condition, and $Mg-SO_4$ type with Mg>Ca>Na>K and $SO_4>HCO_3>Cl>NO_3$. Chemical composition of the stream water was quite irregular during the experimental period. Concentrations of Na, K, $HCO_3$, U, Sr, and Cr decreased by $10{\sim}30%$ during rainy season, caused by dilution effects with rain. The concentration of Ca, Mg, $NO_3$, Cd, and Co increased during the rainy season, caused by more easily dissolved from bedrocks or mine drainage with slightly acidic condition than dry season. The stream water was enriched in Mg, Ca, $HCO_3$, $SO_4$, Al, Fe, Zn, Ni, Co, Cr, Cd, Sr and U. Concentrations of Na, Mg, Ca, $SO_4$, $HCO_3$, Fe, Zn, Ni, Sr, and U decreased linearly with distance from the mine adit. These elements were strongly controlled by dilution of unpolluted water influx and/or adsorption on the clay minerals and iron oxyhydroxide precipitates. This mine area exhibited two main weathering processes ; 1) oxidation with acidification derived from Fe sulphides, and 2) pH buffering due to Ca and Mg carbonate dissolution. This weathering processes were followed by adsorption of metals on iron oxyhydroxides and precipitation.

• Journal of Ginseng Research
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• v.44 no.5
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• pp.717-724
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• 2020

Background: Malignant arrhythmias require drug therapy. However, most of the currently available antiarrhythmic drugs have significant side effects. Ginsenoside Rg2 exhibits excellent cardioprotective effects and appears to be a promising candidate for cardiovascular drug development. So far, the oral toxicity and antiarrhythmic effects of Rg2 have not been evaluated. Methods: Acute oral toxicity of Rg2 was assessed by the Limit Test method in mice. Subchronic oral toxicity was determined by repeated dose 28-day toxicity study in rats. Antiarrhythmic activities of Rg2 were evaluated in calcium chloride-induced arrhythmic rats. Antiarrhythmic mechanism of Rg2 was investigated in arrhythmic rats and H9c2 cardiomyocytes. Results: The results of toxicity studies indicated that Rg2 exhibited no single-dose (10 g/kg) acute oral toxicity. And 28-day repeated dose treatment with Rg2 (1.75, 3.5 and 5 g/kg/d) demonstrated minimal, if any, subchronic toxicity. Serum biochemical examination showed that total cholesterol in the high-dose cohort was dramatically decreased, whereas prothrombin time was increased at Day 28, suggesting that Rg2 might regulate lipid metabolism and have a potential anticoagulant effect. Moreover, pretreatment with Rg2 showed antiarrhythmic effects on the rat model of calcium chloride induced arrhythmia, in terms of the reduced duration time, mortality, and incidence of malignant arrhythmias. The antiarrhythmic mechanism of Rg2 might be the inhibition of calcium influx through L-type calcium channels by suppressing the phosphorylation of Ca²⁺/calmodulin-dependent protein kinase II. Conclusion: Our findings support the development of Rg2 as a promising antiarrhythmic drug with fewer side effects for clinical use.