• The Korean Journal of Pharmacology
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• v.31 no.1 s.57
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• pp.63-74
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• 1995

It has been known that, during hypoxia, the adrenal medulla is activated to release catecholamines (CA) while hypoxia also inhibits high $K^+$ -induced CA secretion in the cultured bovine adrenal chromaffin cells. The present study was attempted to examine the effect of hypoxia on CA secretion evoked by chlinergic stimulation and membrane-depolarization from the isolated perfused rat adrenal glands and also to clarify its mechanism of action. For this purpose, using the isolated rat adrenal glands, the effects of hypoxia on CA release evoked by nicotinic ($N_1$) and muscarinic ($M_1$) receptor agonists, membrane-depolarizing agent, $Ca^{++}$-channel activator, intracellular $Ca^{++}$-releaser and ACh were determined. Experiments were carried out, perfusing Krebs solution pre-equilibrated with a gas mixture of 95% N_2$ and 5% $CO_2$. Hypoxia was maintained for $3{\sim}4$ hours through the experiments. Hypoxia gradually caused a time-dependent seduction in CA secretion evoked by DMPP ($100{\mu}M$), McN-A-343 ($100{\mu}M$), ACh (5.32 mM), Bay-K-8644 ($10{\mu}M$) and high $K^+$ (56 mM) respectively. How-ever, it did not affect CA secretion evoked by cyclopiazonic acid ($10{\mu}M$). Hypoxia itself also did fail to produce any influence on spontaneous secretory response of CA. These experimental results suggest that hypoxia depresses CA release evoked by both cholinergic stimulation and membrane-depolarization from the isolated rat adrenal medulla, and that this inhibitory activity may be due to the result of the direct inhibition of $Ca^{++}$ influx into the chromaffin cells without any effect on the calcium mobilization from the intracellular store.

• The Korean Journal of Pharmacology
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• v.23 no.1
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• pp.33-44
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• 1987

NADPH oxidase dependent superoxide generation and phagocytosis in neutrophils stimulated with opsonized zymosan or heat aggregated IgG were coincided with the process of calcium uptake. The responses in activated neutrophils were enhanced with increasing concentrations of extracellular calcium and these effects were significantly inhibited by calcium chelators, EGTA and EDTA. The superoxide generation in activated neutrophils was reduced by dantrolene and chlorpromazine. Calcium antagonists, bepredil, diltiazem, verapamil, nifedipine and nimodipine effectively inhibited the calcium uptake, superoxide generation and phagocytosis in activated neutrophils, and NADPH oxidase activity was also inhibited. The results suggest that calcium antagonists may inhibit the superoxide generation and phagocytosis in activted neurtophils by the inhibition of calcium influx and by the action on intracellular redistribution of calcium and NADPH oxidase system.

• Journal of Microbiology and Biotechnology
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• v.28 no.1
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• pp.12-21
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• 2018

Photorhabdus temperata (PT), a gram-negative bacterium, lives symbiotically within entomopathogenic nematodes. The insecticidal compounds derived from Photorhabdus are used as biopesticides in agriculture. However, the physiological properties are not well characterized. In the course of our screening for neuroprotective and anti-neuroinflammatory substances from natural products, the culture broth of PT showed considerable activities. By activity-guided purification, five anthraquinones, namely, 3-methoxychrysazine (1), 1,3-dimethoxy-8-hydroxy-9,10-anthraquinone (2), 1,3,8-trihydroxy-9,10-anthraquinone (3), 3,8-dihydroxy-1-methoxy-9,10-anthraquinone (4), and 1,3,4-trimethoxy-8-hydroxy-9,10-anthraquinone (5), were isolated from the ethyl acetate fraction of the PT culture broth. Among the isolated compounds, $75{\mu}M$ 3 significantly protected mouse hippocampal neuronal cells (HT22) against 5 mM glutamate-induced cell death via the inhibition of reactive oxygen species production, $Ca^{2+}$ influx, and lipid peroxidation. Additionally, 3 and 4 effectively suppressed the interferon-${\gamma}$-induced neuroinflammation of mouse-derived microglial cells (BV2) at 10 ng/ml, via the reduction of nitric oxide, interleukin-6, and tumor necrosis factor-${\alpha}$. Anthraquinones 3 and 4 derived from the PT culture broth are a potential starting point to discover neuroprotective and anti-neuroinflammatory drug leads. The novel compound 5 is reported for the first time in this study.

• Preventive Nutrition and Food Science
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• v.15 no.3
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• pp.189-195
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• 2010

Water extracts from 20 medicinal plants, traditionally used for postmenopausal symptoms in Korea, were examined for their vasorelaxant activity in isolated rat thoracic aorta rings precontracted with norepinephrine (NE). Among the 20 medicinal plants, Cornus officinalis (CoEx, 0.3 mg/mL), Schisandra chinensis (ScEx, 0.3 mg/mL), Erythrina variegate (EvEx, 0.3 mg/mL), and Epimedium koreanum (EkEx, 0.3 mg/mL) showed rapid relaxation of endothelium-intact aorta ($69\pm4%$, $40\pm3%$, $25\pm2%$, and $23\pm3%$ of active tone induced by NE, respectively). In contrast, the extracts of Erythrina variegata (EvEx), Angelica gigas (AgEx), Pueraria thunbergiana (PtEx), and EkEx lead to gradual (i.e., long-term) relaxation to baseline in endothelium-intact vessels. The time to complete relaxation was 20～40 min. These 6 plant extracts were selected for the investigation of possible underlying mechanisms. The CoEx-, ScEx-, or EkEx-induced rapid relaxations were virtually abolished by endothelium denudation, and were significantly inhibited by pretreatment with nitric oxide (NO) synthase inhibitor $N^G$-nitro-L-arginine (L-NNA, 10 ${\mu}M$), indicating that increased formation of NO might contribute to the endothelium-mediated relaxation. In long-term responses, the endothelium denudation did not affect PtEx-induced relaxation, whereas it delayed responses by EvEx and AgEx, and significantly inhibited the effect of EkEx. Among EvEx, AgEx, and PtEx, EvEx attenuated the $CaCl_2$-induced vasoconstriction in high-potassium depolarized medium, implying that EvEx is involved in inhibition of the extracellular calcium influx to smooth muscle through voltage dependent calcium channels. These results provide the scientific rationale for the interrelationships between the use of 20 medicinal plants and their effects on cardiovascular health in estrogen deficient conditions.

• 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

• Journal of Life Science
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• v.16 no.2 s.75
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• pp.315-322
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• 2006

FS11052, a novel microbial metabolite from Streptomyces spp. was identified as a small molecular substance and shown inhibition activities for the release of neurotransmitter from rat hippocampal neuron and PC12 cells. FS11052 is an inhibitor of tritiated norepinephrine ($[^3H]-NE$) release in high $K^+$ buffer solution containing ionomycin, indicating that FS11052 inhibits neurotransmitter release after the influx of $Ca^{2+}$ ions. When examined the effect of FS11052 on glucuronidase release from guinea pig neutrophils, FS11052 inhibited glucuronidase release: when treated with $5{\mu}g/ml$ of FS11052, which was not induced cellular cytotoxicity. The fact that the glucuronidase release in neutrophil and norepinephrine release in neuron was inhibited suggests the similarity in the locations and the mechanisms of FS11052 action targets. When treated with $5{\mu}g/ml$ of FS11052, $[^3H]-NE$ release and neurite extension for both rat hippocampal neurons and PC12 cells were prevented. These observations of FS11052 functioning as an inhibitor of neurotransmitter release suggest that FS11052 has an important role in synaptic transmission in neuron.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.189-206
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• 1988

The effects of ouabain on the contractile and electrical activities were investigated in the isolated preparations of guinea-pig taenia coli, and compared with those of vanadate. Spontaneous contractions were recorded with force transducer, and electrical activites were measured by use of suction electrode, or single sucrose-gap technique. The contractions were induced by the electrical stimulation for 5 seconds every 1 minute with alternating current (60 Hz, 3.0 V/cm) through the platinum electrodes located in parallel with the long axis of the preparation. All experiments were performed in tris-buffered Tyrode solution which was aerated with $100%{\;}O_2$ and kept at $35^{\circ}C$. The results obtained were as follows: 1) Responses of spontaneous contractions to ouabain were concentration-dependent; $10^{-7}M$ ouabain caused a rise of basal tone. Above the concentration of $10^{-6}M$ ouabain, an initial increase followed by a decrease in tension was observed. 2) A continuous spike discharge was induced by the administration of $10^{-7}M$ ouabain. Above $10^{-6}M$ ouabain, a transient initial increase followed by a decrease in spike frequency and amplitude was produced, and finally membrane potential was sustained at a certain level without a spike discharge. 3) The characteristic response to $10^{-7}M$ ouabain was not blocked by the pretreatment with $10^{-7}M$ atropine. 4) The electrically induced contractions were completely suppressed at the concentration of $2{\times}10^{-7}M$ ouabain. These contractions were blocked more rapidly in paralled with the increase in ouabain concentration. 5) Effects of vanadate on the spontaneous activities were quite different from those of ouabain; $10^{-6}M$ vanadate increased the amplitude of contractions and $10^{-5}M$ vanadate increased slightly both amplitude and frequency of spontaneous contractions. $10^{-4}M$ vanadate showed irregular phasic contractions superimposed on the increased basal tone. 6) $10^{-5}M$ vanadate depolarized the membrane potential and shortened the interval between the bursts of spike discharge, whereas $10^{-4}M$ vanadate induced continuous spike discharge with membrane depolarization. 7) Vanadate caused a characteristic inhibitory response to the contractions induced by electrical stimulation; An initial rapid inhibition of tension development and then gradual recovery to a certain level. From the above results, the following conclusions could be made: 1) The rise of basal tone at $10^{-7}M$ ouabain is due to continuous spike discharge without a silent period. The continuous spike discharge is likely to be associated with a slight membrane depolarization caused by the blockage of Na pump. 2) The biphasic response induced by above $10^{-6}M$ ouabain seems to occur by the different mechanisms. The initial increase in tension is associated with depolarization along with an increase in spike frquency, whereas the subsequent relaxation occurs through a non-electrical mechanism. 3) The characteristic response to $10^{-7}M$ ouabain is resulted not from the action on intrinsic nerve terminal, but from its direct action on the membrane of smooth muscle cells. 4) The phasic contractions superimposed on the increased basal tone at the concentration of $10^{-4}M$ vanadate is resulted from the continuous spike discharge with membrane depolarization, of which mechanism remains unknown. 5) The inhibitory action of ouabain on the electrically induced contractions suggests that the increasein intracellular Na in some way inhibits the electrically induced $Ca^{2+}$ influx. The mechanism of vanadate action on the induced contractions remains unknown.