• Korean Journal of Veterinary Research
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• v.43 no.3
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• pp.373-382
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• 2003

Magnesium ion ($Mg^{2+}$) is a vasodilator, but little is known about its mechanism of action on vascular system. In vitro, extracellular magnesium sulfate ($MgSO_4$) produced relaxation in phenylephrine (PE) or high KCl-precontracted isolated rat thorocic aorta with (+E) or without (-E) endothelium in a concentration-dependent manner. The $MgSO_4$-induced relaxations were not affected by removal of the endothelium. Pretreatment of +E or -E aortic rings with nitric oxide synthase (NOS) inhibitors ($20{\mu}M$ L-NNA, $100{\mu}M$ L-NAME, $1{\mu}M$ dexamethasone and $400{\mu}M$ aminoguanidine), cyclooxygenase inhibitor ($10{\mu}M$ indomethacin), guanylate cyclase inhibitors ($10{\mu}M$ ODQ and $30{\mu}M$ methylene blue) and $Ca^{2+}$ transport blocker ($10{\mu}M$ ryanodine) did not affect the relaxant effects of $MgSO_4$. $Ca^{2+}$ channel blockers ($0.3{\mu}M$ nifedipine and $0.5{\mu}M$ veropamil) completely decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. However, in $Ca^{2+}$-free medium, $MgSO_4$-induced vasorelaxation was potentiated and this response was inhibited by nifedipine. Protein kinase C (PKC) inhibitors ($1.0{\mu}M$ staurosporine, $0.5{\mu}M$ tamoxifen and $0.1{\mu}M$ H7) or PLC inhibitor ($100{\mu}M$ NCDC) markedly decreased the relaxant effects of $MgSO_4$ in +E and -E aortic rings. In vivo, infusion of $MgSO_4$ elicited significant decreases in arterial blood pressure. After intravenous injection of nifedipine ($150{\mu}g/kg$) and NCDC (3 mg/kg), infusion of $MgSO_4$ inhibited the $MgSO_4$-lowered blood pressure markedly. However, after introvenous injection of saponin (15 mg/kg), L-NNA (3 mg/kg), L-NAME (5 mg/kg), indomethacin (2 mg/kg), methylene blue (15 mg/kg) and aminoguanidine (10 mg/kg) failed to inhibit it. These results suggest that endothelial NQ-cGMP or prostaglandin pathway is not involved in vasorelaxant or hypotensive action of $Mg^{2+}$ and that these effects are due to the inhibitory action of $Mg^{2+}$ on the $Ca^{2+}$ channel or PLC-PKC pathway, and are due to the competitive influx of $Mg^{2+}$ and $Ca^{2+}$ through the $Ca^{2+}$ channel.

• The Korean Journal of Physiology and Pharmacology
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• v.9 no.2
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• pp.87-94
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• 2005

It is not clear whether $Ca^{2+}-induced$ $Ca^{2+}$ release from the sarcoplasmic reticulum (SR) is involved in the regulation of atrial natriuretic peptide (ANP) release. Previously, we have shown that nifedipine increased ANP release, indicating that $Ca^{2+}$ entry via voltage-gated L-type $Ca^{2+}$ channel activation decreases ANP release. The purpose of the present study was two-fold: to define the role of SR $Ca^{2+}$ release in the regulation of ANP release and whether $Ca^{2+}$ entry via L-type $Ca^{2+}$ channel is prerequisite for the SR-related effect on ANP release. Experiments were performed in perfused beating rabbit atria. Ryanodine, an inhibitor of SR $Ca^{2+}$ release, increased atrial myocytic ANP release ($8.69{\pm}3.05$, $19.55{\pm}1.09$, $27.31{\pm}3.51$, and $18.91{\pm}4.76$% for 1, 2, 3, and $6{\mu}M$ ryanodine, respectively; all P<0.01) with concomitant decrease in atrial stroke volume and pulse pressure in a dose-dependent manner. In the presence of thapsigargin, an inhibitor of SR $Ca^{2+}$ pump, ryanodine-induced increase in ANP release was not observed. Thapsigargin attenuated ryanodine-induced decrease in atrial dynamic changes. Blockade of L-type $Ca^{2+}$ channel with nifedipine abolished ryanodine-induced increase in ANP release ($0.69{\pm}5.58$% vs. $27.31{\pm}3.51$%; P＜0.001). In the presence of thapsigargin and ryanodine, nifedipine increased ANP release and decreased atrial dynamics. These data suggest that $Ca^{2+}$-induced $Ca^{2+}$ release from the SR is inversely involved in the regulation of atrial myocytic ANP release.

• 전기의세계
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• v.41 no.12
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• pp.21-30
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• 1992

내연기관의 가솔린자동차보다 역사가 오래된 전기자동차는 상대적으로 주생성능과 가격 경쟁력의 열세로 그 자취를 감추었고 최근까지 주로 특수목적의 단거리 저속차량으로 사용되고 있다. 그러나 1890년대 후반부터 전세계가 자동차배기가스에 의한 대기오염과 지구온난화 현상등의 문제를 심각하게 공감하게 되었고 마침내 미국 캘리포니아주에서는 전가자동차의 강제판매를 규정화하게 이르렀다. 이 규정에 의하면 1998년도부터 차량 판매대수의 2%를 전기자동차 판매로 강제요구하고 있다. 이 비율은 2000녀도에 5% 2003년에는 10%로 늘어날 계획이다. 따라서 미국에 많은 자동차를 수출하고 있는 일본, 독일 및 여러 유럽국가에서는 이 사업에 막대한 자금을 투자하며 개발에 몰두하고 있다. 미국의 Big3도 에너지성의 도움으로 최근 USABC를 결성하여 전기자동차 개발에 박차를 가하고 있다. 지금까지 기존의 가솔린자동차 기술에 있어서 일본과 독일에 상대적 열세에 있었던 미국도 이번 캘리포니아주의 전기자동차 강제판매 규정에 따른 전기자동차 사업으로 미국자동차 시장의 새로운 판도를 조성하겠다는 의도인듯하다. 국내에서도 정부가 이 사업의 중요성을 심각히 인식하고 G7사업과제의 하나로 선정하여 산, 학, 연 각층의 전문가가 참여하여 성공적으로 개발을 마칠 수 있도록 적극 지원하고 있다. 지금까지의 평균주행성능을 보면 최고속도 100-120km/h, 일층전 최대주행거리 150-200km 정도이며, 아직 양산체제에 돌입하지 않았기 때문에 가격면에서 경쟁력이 없는 실정이다. 그러나 1990년도에 들면서 각종 요소부품들의 기술수준이 급성장을 이루어서 앞으로 10년정도 후면 성능과 가격면에서 가솔린자동차와 대등한 수준의 전기자동차 개발이 실현될 수 있으리라 예측된다.는 영향받지 않았다. Clonidine의 심박수 감소작용은 .뇌실내및 정맥내 diltiazem이나 nifedipine 처리후에 감약되었다. 5). 뇌실내 clonidine$(30{\mu}g)$ 처 리후 뇌실내 diltiazem$(400{\mu}g)$과 nifedipine$(350{\mu}g)$의 혈압하강및 심박수 감소효과는 영향 받지 않고 그대로 나타났다. 이상의 결과로 diltiazem과 nifedipine은 가토뇌내에서 methoxamine에 의한 혈압상승의 작용점인 alrfia-1 adrenoceptor의 흥분에는 영향을 미치지 못하나 clonidine의 작용점인 alpha-2 adrenoceptor의 흥분에 의한 혈압하강및 심박수 감소효과는 억제한다고 추론하였다.thin 함량은 110.6 mg/L로서 산업적인 생산성이 있는 것으로 나타났다. 이번 연구를 통하여 개발된 변이주 B76 및 이의 대량 발효를 위한 최종조건의 정립은 향후 astaxanthin의 산업적 생산공정에 필요한 기초자료로 이용될 것으로 기대된다.색총말내에 소형의 도형, 소형의 장형 연접소포 및 DENSE CORE VESICLE의 3가지 연접소포를 가지고 있었고 출현빈도수는 촉각엽에서 가장 큰 33%이었다. 제5형 신경연접은 축색종말내에 중등도크기의 원형, 대형의 원형연접소포 및 DENSE CORE VESICLE을 포함하였고 13%의 출현빈도수로 관찰되었다. 배추횐나비의 촉각에 있는 지각신경세포가 뇌의 촉각엽으로 뻗어 들어가 위의 5가지 신경연접중 어느 형을 형성하는지를 관찰하기 위하여 좌측 촉각의 기부를 제거하여 지각신경세포를 절단하였는데 그 결과, 좌측 촉각엽에서 제4형의 신경연접이 퇴행성 변화를 나타내었다.

• 대한임상약리학회:학술대회논문집
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• 1993.12a
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• pp.32-32
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• 1993

• Archives of Pharmacal Research
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• v.13 no.4
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• pp.310-313
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• 1990

Hantzsch synthesis of 5-formyluracil (1) methyl acetoacetate (2) and methyl 3-aminocrotonate (3) gave 2, 6-dimethyl-4-(2, 4-dioxo-5-pyrimidy)-1, 4-dihydropyridine-3, 5-dicarboxylic acid dimethylester (4a) in 54.6 yield. As the same procedure, 1, 3-dimethyl-5-formyl-uracil (6) gave 2, 6-dimethyl-4-(1, 3-dimethyl-2, 4-dioxo-5-pyrimidyl)-1, 4-dihydropyridine-3, 5-dicarboxylic acid dimethyl easter (7a) IN 52.2% yield. 4a was methylated to afford 7a also in 52% yield.

• Journal of Microbiology and Biotechnology
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• v.14 no.3
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• pp.456-465
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• 2004

$K^+$ efflux through a certain type of $K^+$ channels causes the change of membrane potential and leads to cAMP synthesis in the transmembrane cell signaling for the initiation of sperm motility in the salmonid fishes. The addition of $Ca^{2+}$ conferred motility to the trout sperm that were immobilized by external $K^+$ and other alkaline metals, $Rb^+$ and $Cs^{2+}$, suggesting the participation of external $Ca^{2+}$ in the initiation of sperm motility. L-type $Ca^{2+}$ channel blockers such as nifedipine, nimodipine, and FS-2 inhibited the motility, but N-type $Ca^{2+}$ channel blocker, w-conotoxin MvIIA, did not. On the other hand, the membrane hyperpolarization and cAMP synthesis were suppressed by $Ca^{2+}$ channel blockers, nifedipine, and trifluoroperazine. Furthermore, these suppressions were relieved by the addition of $K^+$ ionophore, valinomycin. Inhibitors of calmodulin, such as W-7, trifluoperazine, and calrnidazol-C1, inhibited the sperm motility, membrane hyperpolarization, and cAMP synthesis. The results suggest that $Ca^{2+}$ influx through $Ca^{2+}$ channels that are sensitive to specific $Ca^{2+}$ channel blockers and calmodulin participate in the changes of membrane potential, leading to synthesis of cAMP in the cell signaling for the initiation of trout sperm motility.

• Journal of Pharmaceutical Investigation
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• v.37 no.4
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• pp.229-235
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• 2007

Multi-layered granules were prepared by a fluidized-bed coater and uniformed granules were obtained with a size range between $950{\sim}1000{\mu}m$ in diameter. The granule system was composed of three layers, i.e. seed layer with sugar sphere bead and a water-swellable polymer, middle layer with a drug, solubilizer and polymer, and the top layer of porous membrane with a polymeric binder. The aim of this work is to find out the dependence of a drug dissolution rate on the amount of a water-soluble binder and a solubilizer in the granule system. The results showed that the higher amount of hydrophilic binder in the porous membrane, gave the bigger pore size and porosity and made faster dissolution rate and also the higher amount of solubilizer in drug layer enhanced the dissolution rate of drug.

• 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.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.207-218
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• 1988

Effects of 1, 4-dihydropyridine compounds, such as nifedipine, nisoldipine, nitrendipine, and nimodipine which were calcium antagonists on the normal and Ca-dependent, slow channel mediated action potentials in the guinea pig's papillary muscle were investigated. The glass microelectrode was impaled into a papillary muscle cell for measurements of potential changes with the simultaneous tracing of isometric contraction. The concentration of Ca antagonists were 1 mg/l (nifedipine and nisoldipine), 2 mg/l (nitrendipine and nimodipine), which showed the maximal inhibition of isometric contraction (above 90%) and simultaneous effects on the normal action potentials and only the halves of those concentrations were sufficient to observe the effects on the calcium action potentials. The data for analysis were only chosen when the microelectrode was maintained in a cell throughout the experiments. 1, 4-Dihydropyridine compounds decreased the action potential duration but did not affect the resting membrane potential, overshoot, and upstroke velocity of the normal action potentials with the decrease in the isometric contraction. And with the decrease in the area and amplitude of isometric contraction, the area, amplitude, upstroke velocity and duration of Ca action potential was decreased. But the differences in the effects of the Ca antagonists were not observed. Therefore it is inferred that the changes in normal and Ca action potential induced by the 1, 4-dihydropyridine compounds with a common chemical structure would be caused by the slow inward Ca-current, not by a fast Na-current.

• Korean Journal of Veterinary Research
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• v.43 no.4
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• pp.587-595
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• 2003

The aim of this study was to investigate trazodone's effect on vasorelaxation and blood pressure lowering and to examine its underlying mechanism of action in isolated thoracic aorta and anesthesized rats. Precontracted aortic rings with high KCl were relaxed with trazodone, at concentrations of $50{\mu}M$ or greater. However, precontracted rings with phenylephrine (PE) were relaxed with trazodone, at concentrations of $0.03{\mu}M$ or greater, in a concentration-dependent manner. These relaxant effects of trazodone on endothelium intact rat aortic rings were significantly greater than those on denuded rings. The trazodone-induced relaxations were suppressed by nitric oxide synthase (NOS) inhibitors, N(G)-nitro-L-arginine (L-NNA) and N(omega)-nitro-L-arginine methyl ester (L-NAME), guanylate cyclase inhibitors, methylene blue and 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ), a $Ca^{2+}$-activated $K^+$ channel blocker, tetrabutylammonium (TBA), a $Ca^{2+}$ channel blocker, nifedipine, $Na^+$ channel blockers, lidocaine and procaine, and removal of extracellular $Na^+$, but not by aminoguanidine, 2-nitro-4-carboxyphenyl-n, n-diphenylcarbamate (NCDC), indomethacin, glibenclamide and clotrimazole. In vivo, infusion of trazodone elicited significant decrease in arterial blood pressure. Trazodone-induced decrease in blood pressure was markedly inhibited by pretreatment of intravenous injection of saponin, L-NNA, methylene blue, TBA, lidocaine or nifedipine. These findings suggest that the endothelium-dependent relaxation and decrease in blood pressure induced by trazodone is mediated by release of NO from the endothelium, activation of TBA-sensitive $Ca^{2+}$-activated $K^+$ channels or inhibition of $Ca^{2+}$ entry through voltage-gated channel.