• Korean Journal of Environmental Biology
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• v.19 no.2
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• pp.107-112
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• 2001

A tissue biosensor was developed for the continuous determination of $Na^+$ channel blockers. The proposed sensor was applied to the determination of Na+ channel blockers in seaweed. It was found that $Na^+$ channel blocker content displayed seasonal variation; it was high from February to April and decreased thereafter (May - August). From these results the present proposed method may be used for high sensitive determination of $Na^+$ channel blockers contained in the seaweed organisms and environments. Therefore, it may be important to monitor $Na^+$ channel blocker content of seaweed throughout the year.

• Archives of Pharmacal Research
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• v.25 no.3
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• pp.349-356
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• 2002

The present study was performed to examine the effect of fangchinoline, a bis- benzylisoquinoline alkaloid, which exhibits the characteristics of a $Ca^{2+}$ channel blocker, on cyanide-induced neurotoxicity using cultured rat cerebellar granule neurons. NaCN produced a concentration-dependent reduction of cell viability, which was blocked by MK-801, an N-methyl-D-aspartate (NMDA) receptor antagonist, verapamil, L-type$Ca^{2+}$channel blocker, and L-NAME, a nitric oxide synthase inhibitor. Pretreatment with fangchinoline over a concentration range of 0.1 to 10 $\mu$M significantly decreased the NaCN-induced neuronal cell death, glutamate release into medium, and elevation of $[Ca^{2+}]_i$ and oxidants generation. These results suggest that fangchinoline may mitigate the harmful effects of cyanide-induced neuronal cell death by interfering with $[Ca^{2+}]_i$influx, due to its function as a $Ca^{2+}$ channel blocker, and then by inhibiting glutamate release and oxidants generation.

• Biomolecules & Therapeutics
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• v.9 no.1
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• pp.26-32
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• 2001

This study was investigated about the effect of glibenclamide (GLY) which is $K^{+}$ channel blocker on renal function in rabbit, GLY, when given into the vein, produced the diuretic action accompanied with the increases of amounts of N $a^{+}$ and $K^{+}$ excreted into urine ( $E_{Na}$ , $E^{K}$), and then osmolar and negative free water clearances ( $C_{osm}$, $T^{C}$$_{H2O}$), fraction excretory rates of filtered N $a^{+}$ and $K^{+}$ ( $F_{Na}$ , $F_{K}$) and ratios of $E_{K}$ against $E_{Na}$ were augmented. Filtration fraction (FF) were reduced because renal plasma flow (RPF) were not changed but glomerular filtration rates (GFR) were diminished. GLY administered into a renal artery exhibited significant reduction of urine volume along with the decreases of GFR and RPF in only experimented kidney whereas changes of renal function was not observed in control kidney. GLY given intracerebroventricularly exhibited diuretic action along with the increase of $E_{Na}$ , $E_{K}$ and $F_{Na}$ , $F_{K}$ by small dose which was not affect on renal function when it given into the vein. Above results suggest that GLY given into the vein in rabbit produce the diuretic action by inhibition of electrolytes reabsorption in renal tubules through central function. function.n. function.ion.

• KSBB Journal
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• v.13 no.1
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• pp.71-76
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• 1998

Tissue biosensor for mearsuring sodium channel blockers, such tetrodotoxin(TTX), saxitoxin (STX) and paralytic shellfish poisoning(PSP) consisted of frog bladder membrane, and $Na^{+}$ electrode. The proposed biosensor was applied to determine Chinese drug and dry or wet Porphyra yezonesis $Na^{+}$ channel blockers below the detection limit of the standard mouse bio-assay while the observed detection limit didn't cause human poisoning. The proposed biosensor system may be used for future $Na^{+}$ channel blockers monitoring within the marine environment.

• Korean Journal of Clinical Pharmacy
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• v.19 no.2
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• pp.167-179
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• 2009

Hypertension is one of the most common chronic diseases and it causes cardiovascular and cerebrovascular disease. While antihypertensive drug use increased, it took 15% of national health insurance drug expenditure. This study aimed to examine the pattern of antihypertensive drug prescription using National Health Insurance claims database and compare it with recommendations of Korea Hypertension Treatment Guidelines. Among the antihypertensive drugs, calcium channel blocker(64.4%) was most commonly prescribed class, and diuretics(44.6%), angiotensin II receptor blocker(33.3%), angiotensin converting enzyme inhibitor(11.7%) was followed. Approximately 81% of antihypertensives prescription were without cardiovascular or cerebrovascular disease, and among the comorbid conditions, diabetes(10.7%) was most common. calcium channel blocker(62.3%) was mostly prescribed class for hypertension with angina pectoris, angiotensin receptor blocker(45.3%) with myocardial infarction, diuretics(70.2%) and calcium channel blocker(49.5%) with congestive heart failure. For Hypertension with cerebrovascular disease, calcium channel blocker(68.0%) and angiotensin receptor blocker(43.3%) were prescribed mainly. When it comes to diabetes, calcium channel blocker(57.2%) was still mostly prescribed and angiotensin receptor blocker(45.9%) followed. But in hospitals and tertiary hospitals, angiotensin receptor blocker(65.7, 66.1%) was mostly prescribed for the patients with diabetes. For Hypertension with chronic renal disease, angiotensin receptor blocker(59.5%), calcium channel blocker(56.5%), diuretics(54.6%) were mainly used. Average number of classes per prescribing was $1.89{\pm}0.89$ class, average days per prescribing was $33{\pm}19$ day. Among the hypertension without comorbidity, 40.5% of prescription was monotherapy and 58.8% of polytherapy included diuretics. Among the outpatient prescriptions, calcium channel blocker was the most commonly used class, and the prescription pattern in clinic did not closely followed recommendations of Hypertension Treatment Guidelines.

• Biomolecules & Therapeutics
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• v.7 no.3
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• pp.249-256
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• 1999

Glibenclamide(GLY)(1.0 and 3.0 mg/kg), an ATP-dependent $K^+$ channel blocker, when given into the vein in dogs, produced the diuretic action accompanied with the increase of osmolar clearance($C_{osm}$), urinary excretion of $Na^+$ and $K^+$ ($E_{Na}$, $E_K$), and with the decrease in reabsorption rates for $Na^+$ and $K^+$ in renal tubules ($R_{Na}$, $R_K$), and then ratios of $K^+$ against $Na^+$($K^+$/$Na^+$) were decreased. GLY did not affect mean arterial pressure at any doses used. At a low dose(0.1 mg/kg), GLY injected into a renal artery brought about the diurectic action in both experimental and control kidney, however at a higher dose(0.3 mg/kg), GLY appeared significant diuretic action in the control kidney, but not in experimental kidney and the decrease of glomerular filtration rates(GFR), renal plasma flow(RPF), $E_K$, and the increase in $E_{Na}$. In the control kidney, these changes in renal function exhibited the same aspect as shown in intravenous experiments. In experiments given into carotid artery of GLY(0.5 and 1.5 mg/kg), changes in all renal function included the increase in urine volume were the same pattern as shown in intravenous experiments. The above results suggest that glibenclamide produces diuretic action through central function and the action site of the GLY in kidney is the renal distal tubules in dogs.

• Advances in Traditional Medicine
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• v.4 no.3
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• pp.157-161
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• 2004

We showed the effects of the traditional herbal medicine, Jukyeoondam-tang (JO-T, Zhu-ru-Wen-Dan-Tang in Chinese), on ventricular arrhythmia induced by aconitine. Electrophysiological experiments with conventional microelectrode techniques revealed that JO-T potently suppressed the aconitine-induced arrhythmias in ventricular strips of the rat. In the aconitine-induced arrhythmia model of the rat, pretreatment with JO-T $(100\;{\mu}g/ml)$ completely occluded the appearance of ventricular tachyarrhythmia (VT) or ventricular fibrillation (VF) induced by aconitine. Furthermore, the aconitine-induced ventricular arrhythmia was occluded by $Na^+$ channel blocker quinidine but was not occluded by $K^+$ channel blocker glibenclamide $(3\;{\mu}mol/L)\;and\;Ca^{2+}$ channel blocker nifedipine $(10\;{\mu}mol/L)$. We also confirmed the effect of JO-T in the ischemia-reperfusion (I/R)-induced arrhythmia model of the rat. JO-T did not affect the I/R-induced arrhythmias in rats. JO-T may alleviate the risk of ventricular arrhythmias following aconitine. These results suggest that JO-T is a potent antiarrhythmic drug having a$Na^+$ channel-blocking action.

• Proceedings of the Korean Society of Applied Pharmacology
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• 1993.04a
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• pp.160-160
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• 1993

목적: Guinea pig heart의 ATP sensitive $K^{＋}$ channel xenopus oocyte에 발현시켜 연구하고져 본 실험을 행하였다. 실험방법: 기니픽 심장으로부터 ,RNA를 분리하여 50ng/$\mu$l의 농도로 50nl를 xenopusdp 주입하였다. Xenpus oocyte에서 conventional electrode를 이용 막전휘를 측정하였고, pH selective 미세전극으로 세포내 pH를 측정하였다. 막전위에 미치는 potassium channel opener, blocker, KCN의 작용을 관찰하였다. 결과: 기니픽 심장 mRNA를 주입하거나 주입하지 않은 xenopus oocyte에서 $K^{＋}$channel opener인 cromakalin, RP49356등은 과분극을 일으키지 못하였다. 그러나 세포내 ATP 감소제인 KCN은 농도 의존적으로 과분극을 일으켰으나 ,glibenclamide에 의해 차단되는 않았다. mRNA를 주입한 oocyte에서 Na-H 자극제인 NH$_4$Cl은 pH 변동을 일으켜 NA-H exchange를 expression 시켰다. 결론: Xenopus oocyte는 cromakalin등에 의해 open되는 $K^{＋}$channel 은 없었고, 기니픽 심근의 ATP sensitive $K^{＋}$channel로 expression 되지 않았으나 Na-H exchange 는 expression 됨을 알 수 있었다. KCN으로 open 되는 $K^{＋}$channel이 있었으나 glibenclamide에는 차단되지 않는 channel이였다.

• The Korean Journal of Physiology
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• v.28 no.2
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• pp.159-167
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• 1994

The contraction of rabbit basilar artery was examined as a function of changes in the $Na^+$ electrochemical gradient in order to determine the contribution of $Na^+/Ca^{2+}$ exchange to the modulation of contractility. Ouabain $(10^{-5}\;M)$ or $K^+-free$ Tyrode solution caused an increase in tonic tension even in the presence of a $Ca^{2+}$ channel blocker $(10^{-6}\;M\;verapamil)$ and an ${\alpha}-receptor$ blocker $(10^{-5}\;M\;phentolamine)$. After treatment with ouabain $(10^{-5}\;M)$, contractions were augmented by reduction of external $Na^+$ concentration. The longer the treatment with ouabain $(10^{-5}\;M)$ was, the larger the amplitude of $Na^+-free$ contracture was. $Na^+-free$ contracture wag induced by either substitution of equimolar Tris for $Na^+$ or substitution of equimolar $Li^+\;for\;Na^+$. The competition between $Na^+\;and\;Ca^{2+}$ for the $Na^+/Ca^{2+}$ exchange carrier would exist, because it was observed that contractility was dependent on the $Na^+$ electrochemical gradient or the extracellular $Ca^{2+}$ concentration (2 mM, 4 mM). Ryanodine $(10^{-7}\;M)$, the blocker of intracellular $Ca^{2+}$ release from the sarcoplasmic reticulum, did not suppress the development of $Na^+-free$ contracture. The contractile response to norepinephrine $(10^{-6}\;M)$ was augmented by reducing the extracellular $Na^+$ concentration. The relaxation rate from caffeine-induced contraction was dependent on the extracellular $Na^+$ concentration (0 mM, 140 mM). From the above results, it could be suggested that $Na^+/Ca^{2+}$ exchange can move $Ca^{2+}$ either into or out of rabbit basilar arterial smooth muscle. $Ca^{2+}$ entry or extrusion is dependent upon the $Na^+$ electrochemical gradient. $Na^+/Ca^{2+}$ exchange plays a significant role in the regulation of contractility in rabbit basilar arterial smooth muscle.

• Journal of Physiology & Pathology in Korean Medicine
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• v.16 no.2
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• pp.389-396
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• 2002

In the present work, we examined the mechanism of vasorelaxant effect of scopoletin, an active constituent of Artemisia capillaris on rat thoracic descending aortic rings. Scopoletin induced a concentration-dependent relaxation in rat thoracic descending aortic rings pre-contracted with phenylephrine (EC/sub 50/ = 238.94±37.4 μM), while it was less effective in rat thoracic descending aortic rings precontracted with high potassium solution (KCI 30 mM). Vasorelaxation by scopoletin was significantly inhibited after endothelial removal, but recovered at high concentration. Pretreatment of rat thoracic descending aortic rings with N/sup G/-nitro-L-arginine (100 μM), a nitric oxide synthase inhibitor, and atropine (1 μM), a muscarinic receptor antagonist, significantly inhibited scopoletin-induced relaxation of rat thoracic descending aortic rings. Neither indomethacin (3 μM), an inhibitor of cydooxygenase, nor propranolol (1 μM), a β -adrenoceptor antagonist, modified the effect of scopoletin. The combination of N/sup G/ -nitro-L-arginine (100 μ M) and miconazole (10 μ M), an inhibitor of cytochrome P 450, did not modify the effect of scopoletin, when compared with pretreatment with N/sup G/-nitro-L-arginine(100 μM) alone. Vasorelaxant effect of scopoletin was inverted by pretreatment with diltiazem (10 μM), a Ca/sup 2+/-channel blocker, at low concentration, while restored at high concentration. Apamin (K/sub ca/-channel blocker, 1 μM), 4-aminopyridine (4-AP, K/sub v/-channel blocker, 1 mM), and tetrodotoxin (TTX, Na/sup +/-channel blocker 1 μM) potentiated the vasorelaxant effect of scopoledn, but glibendamide (K/sub ATP/-channel blocker, 10 μM), tetraetylammonium(TEA, non-selective K-channel blocker, 10 mM) did not affect the relaxation of scopoletin. Free radical scavengers (TEMPO, catalase, mannitol) did not modify vascular tone. These results suggest that nitric oxide, Ca/sup 2+/ -channels play a role in endothelium-dependent relaxations to scopoletin in rat aortas, that apamin, 4-AP, TTX but not glibenclamide, TEA potentiated relaxation to scopoletin mediated by these channels, and that free radicals do not concern to the vasorelaxant effect of scopoletin.