• 한국응용약물학회:학술대회논문집
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• 한국응용약물학회 1995년도 춘계학술대회
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• pp.106-106
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• 1995

A polysaccharide, G009, isolated from Ganoderma lucidum IY009 subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000mg/kg in mice did neither exhibit any abnormal behaviors nor effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guinea-pig ileum and trachea, it did not show any contraction or relaxation at the concentration of 2$\times$10$^{-3}$g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine did not inhibited by the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000mg/kg in rats.

• The Korean Journal of Physiology and Pharmacology
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• 제21권6호
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• pp.591-598
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• 2017

Propofol is known to cause vasorelaxation of several systemic vascular beds. However, its effect on the pulmonary vasculature remains controversial. In the present study, we investigated the effects of propofol on human pulmonary arteries obtained from patients who had undergone surgery. Arterial rings were mounted in a Multi-Myograph system for measurement of isometric forces. U46619 was used to induce sustained contraction of the intrapulmonary arteries, and propofol was then applied (in increments from $10-300{\mu}m$). Arteries denuded of endothelium, preincubated or not with indomethacin, were used to investigate the effects of propofol on isolated arteries. Propofol exhibited a bifunctional effect on isolated human pulmonary arteries contracted by U46619, evoking constriction at low concentrations ($10-100{\mu}m$) followed by secondary relaxation (at $100-300{\mu}m$). The extent of constriction induced by propofol was higher in an endothelium-denuded group than in an endothelium-intact group. Preincubation with indomethacin abolished constriction and potentiated relaxation. The maximal relaxation was greater in the endothelium-intact than the endothelium-denuded group. Propofol also suppressed $CaCl_2$-induced constriction in the 60 mM $K^+$-containing $Ca^{2+}$-free solution in a dose-dependent manner. Fluorescent imaging of $Ca^{2+}$ using fluo-4 showed that a 10 min incubation with propofol ($10-300{\mu}m$) inhibited the $Ca^{2+}$ influx into human pulmonary arterial smooth muscle cells induced by a 60 mM $K^+$-containing $Ca^{2+}$-free solution. In conclusion, propofol-induced arterial constriction appears to involve prostaglandin production by cyclooxygenase in pulmonary artery smooth muscle cells and the relaxation depends in part on endothelial function, principally on the inhibition of calcium influx through L-type voltage-operated calcium channels.

• Biomolecules & Therapeutics
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• 제2권4호
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• pp.369-375
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• 1994

A polysaccharide, G009, isolated from Ganoderma lucidum IY 009, was subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000 mg/kg in mice did not exhibit any abnormal behaviors and another effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000 mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000 mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000 mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60 mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guineapig ileum and trachea, it did not show any contraction or relaxation at the concentrations of 2$\times$10$^{-3}$ g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine were not inhibited at the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000 mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000 mg/kg in rats.

• Journal of Yeungnam Medical Science
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• 제11권2호
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• pp.293-302
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• 1994

유뇨증의 치료제로서 널리 사용되고 있는 imipramine의 작용기전에 관한 학설이 여러가지가 있으나 그 중 콜린성수용체 봉쇄작용을 관찰하기 위한 방법으로 평활근 세포를 분리배양하여 단일세포에 대한 acetylcholine의 수축작용과 이에 대한 imipramine의 길항작용을 atropine의 그것과 비교해 보기로 하였다. 개의 방광을 적출하여 $0{\sim}4^{\circ}C$의 K-H 용액내에서 $2{\times}2mm$크기의 평활근 절편을 얻어 $36^{\circ}C$의 collagenase 용액에 넣고 95%/5% $O_2/CO_2$, 혼합산소 공급하에서 17~20분동안 배양하여 분리된 부유세포군을 5 ml test tubes에 나누어 담고 acetylcholine을 $10^{-14}M{\sim}10^{-9}M$의 농도로 첨가하였다. Acrolein 1%를 가하여 수축한 세포를 고정시킨 후, 위상차 현미경에 장착한 CCTV camera로 채취한 영상을 microscaler로 전송하고 monitor상에서 세포의 길이를 측정하였다. 분리된 세포들은 acetylcholine에 의해 5초 이내에 최대 수축을 보였으며 이후 120초까지 수축상태를 지속하였다. Atropine은 acetylcholine 유발 수축을 atropine $10^{-7}M$ 에서부터 농도의존적으로 억제하였으며, imipramine도 acetylcholine 유발수축을 atropine과 같은 경향으로 농도의존적으로 억제하였는데, imipramine $10^{-9}M$의 저농도에서도 유의한 억제를 보였다. 이상의 결과를 종합하면 본 실험에 사용된 조건하에서의 collagense를 이용한 세포 분리법은 단일세포를 대상으로 하는 실험을 위하여 가용한 방법이며, imipramine은 개의 방광평활근 단일세포에서 atropine보다 더 강력한 콜린성 수용체 봉쇄작용을 나타낸다고 생각되었다.

• 대한약리학회지
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• 제14권1_2호
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• pp.1-11
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• 1978

가토 심실근에서 추출한 mitochondria에서 $Na^+$ 및 $K^+$이온에 의한 $Ca^{++}$ 유리작용을 관찰하였다. 반응액에 첨가한 1-3mM의 소량 $Na^+$은 mitochondria막에 미리 결합되어있던 $Ca^{++}$을 현저히 유리시켰으며, $K^+$은 단독으로는 $Ca^{++}$ 유리를 유도하지 않았으나 $Na^+$에 의한 $Ca^{++}$ 유리에 대하여는 $Na^+/K^+$비에 따라 그것이 클수록 $Ca^{++}$ 유리를 증가시켰다. 간 및 신장 mitochondria에서도 $Na^+$에 의하 $Ca^{++}$ 유리현상을 보였으나 심근mitochondria에 비하여 $Na^+$에 대한 감수성이 훨씬 미약하여 약 $1/10{\sim}1/5$에 지나지 않았다. 이와같은 mitochondria의 $Ca^{++}$ 유리현상은 비교적 $Na^+$에 특이한 작용이었으며 다른 일가양이온중에서는 $Li^+$에 의해서만 어느 정도 보였다. 부전심근 mitochondria에서의 $Na^+$에 의한 $Ca^{++}$유리는 정상심근 mitochondria에서와 같았으며 이때 digitalis 강심배당체가 직접적으로는 별 영향을 미치지 않았다. 이상에서 심근의 경우 mitochondria는 세포내 $Ca^{++}$을 조절할 수 있는 기구로서 심근수축의 E-C coupling과정에서 세포막의 전기적 흥분현상과 결부하여 $Ca^{++}$을 유리할 수 있을 것으로 추정하였으며, 한편 digitalis배당체의 강심작용기전에 있어서는 digitalis 배당체에 의한 세포막의 $Na^+$, $K^+$-ATPase 억제결과 초래될 수 있는 세포내의 $Na^+$ 증가 및(또는) $K^+$감소가 간접적으로 mitochondria에서부터 $Ca^{++}$ 유리를 증가하여 E-C coupling 과정을 촉진할 수 있을 것을 사료하였다.

• 대한수의학회지
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• 제34권3호
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• pp.493-500
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• 1994

The purpose of this study was to investigate the effects of neurotransmitters and the source of $Ca^{2+}$ in the effects of neurotransmitters on the motility of pig oviductal isthmic smooth muscle. The motility of the isolated smooth muscle was recorded by using physiological recording system. The results were summarized as follows; Acetylcholine, norepinephrine, histamine and prostaglandin $F_{2{\alpha}}(PGF_{2{\alpha}})$ caused the contraction and the contractile responses were increased in a dose-dependent manner from the concentration of $10^{-7}$ to $10^{-4}M$. The maximum contractility of acetylcholine, norepinephrine, histamine and $PGF_{2{\alpha}}$ was 65.99, 28.66, 83.99 and 47.33% of 100 mM K contraction, respectively. The contractile response induced by acetylcholine$(10^{-6}M)$ was completely blocked by the pretreatment with cholinergic receptor blocker, atropine$(10^{-6}M)$, the contractile response induced by norepinephrine$(10^{-5}M)$ was blocked by the pretreatment with ${\alpha}$-adrenergic receptor blocker, phentolamine$(10^{-6}M)$ but was not blocked and rather increased by the pretreatment with ${\beta}$-adrenergic receptor blocker. propranolol$(10^{-6}M)$, the contractile response induced by histamine$(10^{-6}M)$ was completely blocked by the pretreatment with $H_1$-histaminergic receptor blocker, pyrilamine$(10^{-6}M)$ but was increased by the pretreatment with $H_2$-histaminergic receptor blocker, cimetidine$(10^{-6}M)$. The contractile response induced by acetylcholine$(10^{-6}M)$, norepinephrine$(10^{-5}M)$ and histamine$(10^{-6}M)$ was weakly contracted response in $Ca^{2+}$-free medium, but the contractile response induced by $PGF_{2{\alpha}}(10^{-6}M)$ was disappeared. The contractile response induced by acetylcholine$(10^{-6}M)$, norepinephrine$(10^{-5}M)$ and histamine$(10^{-6}M)$ was powerfully depressed by the pretreatment with $Ca^{2+}$-channel blocker, verapamil$(10^{-5}M)$ but the contractile response induced by $PGF_{2{\alpha}}(10^{-6}M)$ was completely inhibited.

• Tuberculosis and Respiratory Diseases
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• 제38권1호
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• pp.8-15
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• 1991

It has been well known that the integrity of airway epithelium is important in development of bronchial hyperreactivity and bronchial asthma. But the mechanisms involved are still unclear. To evaluate that airway epithelium is able to modulate the contraction of guinea pig tracheal smooth muscle, we investigated the responsiveness of intact and epithelium-denuded tracheal strips to histamine and acetylcholine. And to evaluate whether cyclooxgenase products play a role in this modulatory mechanism, we also investigated the effect of indomethacin pretreatment on the tracheal responsiveness to histamine. Results were as follows: 1) In guinea pig tracheal smooth muscle the presence of airway epithelium significantly reduced the response to histamine. 2) In the presence of indomethacin dose-response curves and $EC_{50}$ values were similar between intact and epithelium-denuded tracheal strips, that is, indomethacin abolished the influence of epithelium on the contracion of tracheal smooth muscle. 3) The response of tracheal smooth muscle to acetylcholine was similar both in the presence and absence of epithelium. These results suggest that airway epithelium of guinea pig may generate an inhibitory signal to decrease the response of tracheal smooth muscle to histamine and cyclooxygenase products may contrbute to the modulation of airway epithelium on the contracion of tracheal smooth muscle.

• 대한한의학회지
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• 제18권2호
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• pp.340-354
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• 1997

Background : The stenosis of the coronary artery results in a decrease in the myocardial oxygen supply, ischemia and infarction. Jakamchotang as a drug of liquid is generally regarded to have the effect of arrythmia, palpitation from Heart disease and promoting the flow of Ki and Blood. Methods : The purpose of this experimental study is to find whether Jakamchotang is effective or not in curing ischemia in isolated perfused rat hearts and to measure the degree of its curing effect. In this study, under the Langendorff apparatus, ischemia was induced in isolated Sprague-Dawley rat hearts by ceasing the perfusion for 20 minites. Subjects were divided into a normal saline orally administered group(control group), an Jakamchotang orally 100mg administered group (sample A), an Jakamchotang orally 300mg administered group (sample B), and an Jakamchotang injection perfused group(sample C). The heart rates, left ventricular pressure, myocardial dilatation/contraction, cardiac perfusion flow and cardiac ezyme(LDH, CPK) of the four group were measured and compared in order to assess the influence of Jakamchotang on isolated perfused rat hearts recovering abillity from ischemia and infarction. results : 1. Heart rates were increased significantly in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group and Jakamchotang injection perfused group on perfusion and reperfusion(p<0.01). 2. Left ventricular pressure were increased significantly in Jakamchotang orally 100mg administered group and 300mg administered and Jakamchotang injection perfused group(p<0.01) in comparison with control group on perfusion, but every group did not significant on reperfusion. 3. While there were no differances in each group's abillities of myocardial dilatation, the ability of myocardial constriction of Jakamchotang 100mg administered group only on perfusion was significantly greater than that of control group(p<0.05). 4. CBF was no significant on perfusion and reperfusion in comparison with control group(N.S.) 5. LDH was not significantly decreased on perfusion, but significactly decreased in Jakamchotang orally 100mg administered group, Jakamchotang orally 300mg administered group on reperfusion. 6. CPK was significantly decreased in Jakamchotang orally 100mg administered group, 300mg administered and Jakamchotang injection perfused group on perfusion(p<0.01), but was not significantly in Jakamchotang 300mg administered group only on reperfusion(P<0.05) Conclusion : According to the result above, Jakamchotang have an effect to recover in the isolated perfused rat hearts. Especially, the effect of Jakamchotang in orally adminstered group is greater than that of Jakamchotang injection perfused group on preischemia. The followings are the two important results of this study: First, the effect of Jakamchotang used traditionally on heart disease was proved statistcally under the Langendorff apparatus. Second, on the basis of this study, the effect of other type medications on myocardial ischemia can be evaluted in further studies.

• Archives of Pharmacal Research
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• 제23권1호
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• pp.72-78
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• 2000

The general pharmacological properties of YJA20379-1 2-dimethylamino-4,5-dihydrothiazolo[4,5:3,4]pyridol[1,2-a]benzoimidazole, a novel proton pump inhibitor with antiulcer activities were investigated in mice, rats, guinea pigs and rabbits. YJA20379-2 at oral doses of 50, 100 and 200 mg/kg did not affect the general behaviour, hexobarbital hypnosis and motor coordination in mice. The drug did not have analgesic or anticonvulsant action at 200 mg/kg. Locomotor activity and body temperature were not influenced at 100 mg/kg. At a concentration up to 2{\times}10^{-4} g/ml$, YJA20379-2 did not produce any contraction or relaxation of isolated preparations, such as the rat fundus, the guinea pig ileum and the rat uterus, and did not antagonize the contractile response to several spasmogens, such as histamine, acetylcholine, serotonin and oxytocin. At dosages up to 200 mg/kg p.o. YJA20379-2 did not affect the pupil size of mice. Intestinal propulsion of mice was not affected up to 200 mg/kg p.o. and the drug did not affect urinary excretion at 100 mg/kg p.o. These results indicate that at dosages up to 100 gm/kg p.o. YJA20379-2 was found not to affect this pharmacological profile. However, at 200 mg/kg the drug lowered body temperature and showed decreased in locomotor activity and urine volume.

• The Korean Journal of Physiology
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• 제27권2호
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• pp.115-122
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• 1993

There is evidence that noradrenaline enhances spontaneous contractions dose-dependently in guinea-pig antral circular muscle. To investigate the mechanism of this excitatory action, slow waves and membrane currents were recorded using conventional microelectrode techniques in muscle strips and the whole cell patch clamp technique in isolated gastric myocytes. On recording slow waves, noradrenaline $(10^{-5}\;M)$ induced the hyperpolarization of the membrane potential, although the shape of the slow waves became tall and steep. Also, spike potentiaIs occurred at the peaks of slow waves. These changes were completely reversed by administration of phentolamine $(10^{-5}\;M),\;an\;{\alpha}-adrenoceptor$ blocker. Noradrenaline-induced hyperpolarization was blocked by apamin $(10^{-7}\;M)$, a blocker of a class of $Ca^{2+}\;-dependent\;K^+$ channels. To investigate the mechanisms for these effects, we performed whole cell patch clamp experiments. Norndrenaline increased voltage-dependent $Ca^{2+}$ currents in the whole range of test potentials. Noradrenaline also increased $Ca^{2+}\;-dependent\;K^+$\;currents, and this effects was abolished by apamin. These results suggest that the increase in amplitude and the generation of spike potentials on slow waves was caused by the activation of voltage-dependent $Ca^{2+}$ channel via adrenoceptors, and hyperpolarization of the membrane potential was mediated by activation of apamin-sensitive $Ca^{2+}\;-dependent\;K^+\;channels$.