• 대한약리학회지
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• 제2권1호
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• pp.21-29
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• 1966

Dichloroisoproterenol(DCI) i; one of the well known ${\beta}$-adrenergic receptor blocking agents. According to Moran and Perkins, DCI has sympathomimetic like action in relatively low concentrations. Fleming and Hawkins confirmed that DCI acts upon the receptors concerned with positive chronotropic and inotropic actions in the heart. Vogins reported that DCI, in concentration of $5{\times}10^{-8}$ to $5{\times}10^{-6}g/ml$, had properties of sympathomimetic amine causing positive inotropic and chronotropic actions in normal rat atria. And James and Nadeau found that DCI had not only adrenergic blocking effect in moderate and higher concentrations, but it also blocked the effect on the sinus node by vagal stimulation and of directly administered acetylcholine in higher concentrations. As stated above by many authors, DCI has complicated actions according to its concentrations. Our aim at the present experiments was to study the effects of DCI to the action of ouabain and acetylcholine upon the excised rabbit atria, as well as to the action of barium chloride and acetylcholine upon the excised rabbit intestine. In addition, Pan ax Ginseng is widely used as tonics in oriental nations, its pharmacological action, however, has not been clearly established. So we atempted to investigate the effects of the water extract of Panax Ginseng to the action of ouabain and DCI upon both atria and intestine. The results obtained were as follows. 1) DCI has a negative inotropic effect on the excised rabbit atria at concentration of $10^{-5}$ and a positive inotropic effect at concentration of $10^{-6}$. 2) DCI (at concentration of $10^{-6}$) potentiates the positive inotropic effect of ouabain upon the excised rabbit atria. 3) DCI antagonizes the action of acetylcholine upon the excised rabbit atria. 4) The water extract of Panax Ginseng, at concentration of $10^{-3}$, decreases the contractile force of rabbit atria, and tends to slightly increase that of rabbit atria at $10^{-4}$. 5) The water extract of Panax Ginseng exhibits a synergistic action with ouabain on the contractile force of rabbit atria. 6) DCI, in concentrations of $10^{-7}{\sim}10^{-6}$, depresses the tone and amplitude of contraction of the excised rabbit intestine. The depression of the intestinal tone markedly appears in pretreatment with reserpine 2mg/kg 24 hours. 7) DCI antagonizes the contractile effect of barium chloride on the excised rabbit atria. 8) DCI has no significant influence on the action of acetylcholine upon the excised rabbit intestine. 9) The series of those evidences indicates that DCI has a sympathomimetic-like action and more over a relaxing action directly on the excised rabbit intestine. 10) The water extract of Panax Ginseng in concentrations of $10^{-4}{\sim}10^{-3}$, has transient depression of the intestinal tone, but later gradually recovers its normal motility: 11) The water extract of Panax Ginseng has a synergistic action with ouabain on the intestinal contractility.

• 약학회지
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• 제24권1호
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• pp.15-25
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• 1980

The investigation is concerned with the action of ginseng saponin on the contractile force in the rat heart and with the elucidation of the mechanism of the action. The effect of total ginseng saponin, ginsenoside Rb$_{1}$ of protopanaxadiol derivatives and ginsenoside Re of protopanaxatriol derivatives on the contractile force in isolated spontaneously beating normal rat heart was investigated. Total ginseng saponin was obtained from white ginseng by the method of Shibata and Namba. Ginsenoside Rb$_{1}$ and ginsenoside Re were isolated by the method of and Han, respectively. Total ginseng saponin exhibited a slight increase of the contractile force. Ginsenoside Rb$_{1}$ increased markedly the contractile force and dose dependent increase in contractile force was observed. However, ginsenoside Re did not increase the contractile force, but it prevented spontaneous decrease of the contractility of the heart. The mixture of the same dose of ginsenoside Rb$_{1}$ and Re showed a slight increase in the contractile force and its effect was similar to that obtained by total ginseng saponin. Pretreatment with propranolol abolished the positive inotropic effect of ginsenoside Rb$_{1}$ and the positive inotropic effect of ginsenoside Rb$_{1}$ was not observed in a reserpinized rat heart. Pretreatment with ginsenoside Re decreased or abolished the positive inotropic effect of epinephrine. Activities of Na+, K+ -ATPase were inhibited by ginsenoside Rb$_{1}$, total ginseng saponin and ginsenoside Re and these inhibitory effects were dose dependent. The results suggest that catecholamine release or inhibition of Na+, K+ -ATPase activities may be involved in the positive inotropic effect of gindenoside Rb$_{1}$. Ginsenoside Re counteracted the positive inotropic effect of ginsenoside Rb$_{1}$.

• 약학회지
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• 제32권6호
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• pp.402-414
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• 1988

In order to clarify the receptor types and mechanisms underlying the positive inotropic effect of dopamine on the mammalian ventricular myocardium, the action potential, its first derivatives and isometric contraction of the rabbit papillary muscle were recorded using a force transducer and glass capillary microelectrodes filled with 3M KCl. The results were as follows; (1) In normal Tyrode solution, the contractile force was increased and duration of action potential was shortened with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (2) The dose-response curve was markedly shifted to the right by pretreatment with reserpine (5mg/kg i.p., 24hrs prior to the experiment). (3) In 19mM $K^+-Tyrode$ solution, the duration of action potential, maximum rate of rise (V_{max}) of action potential and overshoot were significantly increased with increments of dopamine concentration ($10^{-6}-10^{-4}M$). (4) The inotropic effect of dopamine on the rabbit papillary muscle pretreated with reserpine was antagonized by atenolol ($10^{-6}M$), but not by phentolamine ($3{\times}10^{-6}M$). (5) In rabbit papillary muscle partially depolarized by 19mM $K^+-Tyrode$ solution, slow electrical response (calcium mediated action potential) as well as contraction were restored by dopamine ($10^{-4}M$); this restoration was blocked by calcium antagonists ($3{\times}10^{-5}M$ $LaCl_3{\cdot}6H_2O$, $3{\times}10^{-6}M$ diltiazem) or ${\beta}-adrenoceptor$ antagonist ($3{\times}10^{-6}M$ atenolol), but not affected by ${\alpha}-adrenoceptor$ antagonist ($10^{-5}M$ phentolamine, $3{\times}10^{-6}M$ yohimbine) or vascular dopaminergic receptor antagonist ($10^{-5}M$ haloperidol). The above results may be interpreted as that the positive inotropic effect of dopamine through both direct and indirect action are caused by increase in slow inward current ($Ca^{2+}$ influx into themyocardial cell), and the direct action is mainly due to the stimulation of ${\beta}-adrenoceptors$ in the rabbit papillary muscle.

• 대한약리학회지
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• 제22권1호
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• pp.1-23
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• 1986

• The Korean Journal of Physiology
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• 제29권2호
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• pp.203-216
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• 1995

The effects of ${\alpha}_1-adrenergic$ receptor stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force were investigated in ventricular muscles from guinea-pig hearts. Action potentials, intracellular $Na^+$ activity, and twitch force of ventricular papillary muscles were measured simultaneously under various experimental conditions. Stimulation of the ${\alpha}_1-adrenergic$ receptor by phenylephrine produced variable changes in action potential duration, a slight hyperpolarization of the diastolic membrane potential, a decrease in intracellular $Na^+$ activity, and a biphasic inotropic response in which a transient negative inotropic response was followed by a sustained positive inotropic response. These changes were blocked by prazosin, an antagonist of the ${\alpha}_1-adrenergic$ receptor, but not by atenolol, an antagonist of the ${\beta}-adrenergic$ receptor. This indicates that the changes in membrane potential, intracellular $Na^+$ activity, and twitch force are mediated by stimulation of the ${\alpha}_1-adrenergic$ receptor, but not by stimulation of ${\beta}-adrenergic$ receptor. The decrease in intracellular $Na^+$ activity was not observed in quiescent muscles, depending on the rate of the action pontentials in beating muscles. The intracellular $Na^+$ activity decrease was substantially inhibited by tetrodotoxin. However, the decrease in intracellular $Na^+$ activity was not affected by an inhibition of the $Na^+-K^+$ pump. Therefore, the decrease in intracellular $Na^+$ activity mediated by the ${\alpha}_1-adrenergic$ receptor appears to be due to a reduction of $Na^+$ influx during the action potential, perhaps through tetrodotoxin sensitive $Na^+$ channels. Our study also revealed that the decrease in intracellular $Na^+$ activity might be related to the transient negative inotropic response. The intracellular $Na^+$ activity decrease could lower intracellular $Ca^{2+}$ through the $Na^+-Ca^{2+}$ exchanger and thereby produce a decline in twitch force.

• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.88-88
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• 1995

Tetrahydroisoquinoline (THI) compounds have various pharmacological actions in the cardiovascular system. Recently, we have synthesized 1-${\alpha}$-naphthylmethyl-6,7-dihydroxy-1,2,3,4-tetrahydroisoquinoline, YS 49. In the present study, we evaluated the effect of YS-49 on positive inotropic and chronotropic action using isolated rat heart and on blood pressure and heart rate using anesthesized rabbit. Vasodilating action was also assessed in isolated rat thoracic aorta. YS 49, concentration-dependently relaxed rat aorta precontracted with phenylephrine (PE, 0.3 ${\mu}$M) and high potassium (high K$\^$+/, 65.4 mM). The 50% inhibitory concentration (IC$\sub$50/) of YS 49 in PE-induced and high K$\^$+/-induded contraction was 5.36 ${\mu}$M and 2.52 ${\mu}$M, respectively. In isolated rat atria, YS 49 increased both heart rate and force, and in anesthesized rabbit it decreased blood pressure but increased heart rate. In addition, to know the mechanism of action of the compound, propranolol, nonselective ${\beta}$-antagonist, and phentolamine, ${\alpha}$-blocker, were used. Furthermore, a comparison with the effect of higenamine, trimetoquinol on the vasodilating action in rat thoracic aorta was also made. The action of YS 49 was inhibited by the presence of propranolo, not pentolamine. These results indicate that cardiotonic and vasodilatory action of YS 49 is attributable, at least in part, for ${\beta}$-receptor stimulation.

• 대한약리학회지
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• 제17권2호
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• pp.7-16
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• 1981

심근 수축기전에 있어서 중심적인 역할을 하는 칼슘 이온과 Hienamine과의 상호작용을 비교 검토하였고 아울러 이 강심효과에 대하여 칼슘길항제인 란타눔과 verapamil을 사용하여 이에 미치는 영향을 관찰하였다. Higenamine은 적출 가토좌심방근에 대해 심근의 칼슘과 상호보완적인 상승 및 상가작용을 나타내었고 Higenamine $10^{-7}g/ml$은 0.058mM의 칼슘과 동등한 심근 수축증강효과를 나타내었으며 부자부타놀 분획물과 비교할 때 약 1,000배 정도 강력한 강심작용을 나타내었다. 또한 심근세포막의 칼슘유입을 억제한 조건인 란타눔과 verapamil처치시에도 Higenamine은 용량의존적으로 저하된 심근 수축력을 회복시킴으로 미루어 볼 때 Higenamine외 강심작용기전의 일부는 세포막을 통한 칼슘의 유입을 촉진시키는 것일 것으로 추측하였다.

• 약학회지
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• 제55권2호
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• pp.168-171
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• 2011

Chrysosplenol C [5,6-dihydroxy-2-(4-hydroxy-3-methoxyphenyl)-3,7-dimethoxychromen-4-one] is a flavonoid found in Miliusa balansae and Pterocaulon sphacelatum. We have recently shown that chrysosplenol C has positive inotropic effect in isolated rat ventricular myocytes. In the present study, we explored a possible mechanism for the positive inotropic effect of chrysosplenol C by examining intracellular $Ca^{2+}$ transients during action potentials. The intracellular $Ca^{2+}$ transients were measured by confocal $Ca^{2+}$ imaging in field-stimulated single rat ventricular myocytes. Chrysosplenol C (50 ${\mu}M$) significantly increased the magnitudes (${\Delta}F/F_0$) of $Ca^{2+}$ transients (control, $1.08{\pm}0.05$; chrysosplenol C, $1.25{\pm}0.03$; n=8, P<0.01). Half decay time of the action potential-induced $Ca^{2+}$ transient was not altered by chrysosplenol C (50 ${\mu}M$) (control, $154{\pm}6$ ms; chrysosplenol C, $167{\pm}11$ ms; n=21). The $Ca^{2+}$ content in the sarcoplasmic reticulum (SR), measured as caffeine (10 mM)-induced $Ca^{2+}$ transient, was significantly decreased by chrysosplenol C (50 ${\mu}M$). These results indicate that chrysosplenol C increases $Ca^{2+}$ transients without altering $Ca^{2+}$ removal kinetics in ventricular myocytes, providing a possible mechanism for its positive inotropic effect.

• 대한약리학회지
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• 제19권2호
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• pp.9-16
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• 1983

현재 사용되고 있는 강심제로는 디지탈리스 배당체가 유일한 약물이지란 그 안전역이 대단히 좁아서 보다 안전한 강심제의 개발이 요구되고 있다. 최근 강심작용이 현저할 뿐 아니라 안전역이 비교적 넓을 것으로 인정되는 higenamine이 개발되어 그 작용기전을 밝히려는 시도가 많이 있었다. 본 연구에서는 higenamine의 강심작용 기전을 규명하기 위한 연구의 일환으로 수축빈도-수축력 상관관계(interval-strength relationship)에 있어서 1) Rested-state수축력 2) Positive inotropic effect of activation(PIEA) 3) Negative inotropic effect of activation(NIEA)에 대한 higenamine의 영향을 $Ca^{++}$및 epinephrine과 비교 분석하였다. 실험결과 칼슘은 PIEA를 증가시키기 보다는 오히려 NIEA의 소멸을 촉진함으로써 강심작용을 나타내며 epinephrine 및 higenamine은 PIEA를 증가시키고 NIEA에는 거의 영향을 미치지 않았다.

• 대한약리학회지
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• 제17권1호
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• pp.9-15
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• 1981

부자성분중 강심효과를 나타내는 부자부타놀분획의 작용기전을 심근수축기전이 있어서 중심적인 역활을 하는 칼슘이온과의 상호관계에서 검토하였으며 아울러 동물생체내 혈동력학에 대한 영향을 관찰하였다. 부자부타놀분획 적출 고양이 유두근표본의 수축력증가작용에 있어서 심근외칼슘과 상승적이었으며 부자부타놀분획 $10^{-4}g/ml$는 칼슘 0.06mM과 동등한 심근수측증강 효과를 나타내었다. 심근세포막의 칼슘통로 억제약물인 verapamil 존재하에서 저하된 유두근 수축력은 부자부타놀분획에 의하여 용량의존적으로 회복되었으며, 이로부터 부자부타놀분획의 강심작용기전의 일부는 심근세포막의 완만내향성 칼슘통로를 통한 칼슘유입을 측진하는 것과 관계가 있을 것으로 추측하였다. 정상가토의 혈동력학에 있어서 부자부타놀분획은 디지탈리스배당체와는 달리 용량의존적으로 전신동맥압을 저하시키고, 경동맥혈류량을 증가시켰으며, 심박동수에는 크게 의미있는 변화를 보이지 않았다.