• Biomolecules & Therapeutics
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• v.11 no.1
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• pp.41-50
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• 2003

General pharmacological properties of DA-8159, a new pyrazolopyrimidinone derivative were examined in laboratory animals to investigate its safety profile. The oral administration of DA-8159 (1, 5 or 30 mg/kg) in mice and rats had no effect on general behaviors and central nervous system of the animals in test systems, such as hexobarbital-induced sleeping time, motor coordination, normal body temperature, writhing syndromes induced by 0.75% acetic acid solution, chemo-shock produced by pentetrazole solution and rotar rod test. Anesthetized cats treated intravenously with DA-8159 (0.1, 0.3, 1, 3 or 10 mg/kg) showed transient and mild decrease in blood pressure. However, heart rate, respiration rate and tidal volume were not changed by intravenous DA-8159. In the isolated organs including ileum, heart (sinus rate of atria and contractility of papillary muscle), trachea of guinea pigs and phrenic nerve of rats, DA-8159 ($10^{-8}$ ∼$10^{-5}$ mg/L) did not elicit any effect or inhibitory action on the chemically or electrically stimulated contraction. DA-8159 did not influence gastric secretion, pH and total acid output in rats and intestinal propulsion in mice. The administration of DA-8159 in rats had no effect on the platelet aggregation induced by ADP in rabbit plasma, urinary volume and electrolyte ion ($Na^{+}$, $K^{+}$, $Cl^{-}$) excretion in rats. Prothrombin time (PT) of the rats showed a mild but significant increase after administration of DA-8159. Activated partial thromboplastin time (APTT), however, was not affected by DA-8159. These results indicate that DA-8159 does not exert any of serious pharmacological effects.

• Biomolecules & Therapeutics
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• v.5 no.4
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• pp.369-375
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• 1997

General pharmacological effects of SB-31$^{R}$, the extracts of Pulsatilla koreana, were investigated in mice, rats and guinea-pigs. Intravenous injection of SB-31 (3 and 6 ml/kg) produced almost no effect on central nervous system no effects on the general symptom and behaviors of mice, spontaneous locomotor activity, pentobarbital- induced sleeping time , rotared performance , electroshock and pentylenetertrazole -induced seizures, acetic acid-induced writhing and normal body temperature in mice. SB-31 showed little effects on the spontaneous movement of the isolated ileum and contraction induced by agonists in isolated ileum, suggesting no influence on autonomic nervous system. Administration of SB-31 also did not show any effect on blood pressure in conscious rats. However, a slight decrease in heart rate was observed at high doses (6 and 10 ml/kg) of SB-31 in conscious rats. Similarly, a slight increase in respiratory rate was observed at 6 m1/kg of SB-31 in anesthetized rats. SB-31 did not produce any effect at the dose of 3 ml/kg, but showed a tendency to increase the urinary volume at 6 ml/kg, and produced a decrease in urinary excretions of N $a_{+}$and $K_{+}$at 6 ml/kg. However, transport capacity within the gastrointestinal tract and the secretion of the gastric juice were not influenced by 6 ml/kg of SB-31. In conclusion, these results suggest that SB-31 did not pro-duce any acute effects on the central nervous system, autonomic nervous system, respiratory and circulatory systems, digestive system and kidney function at the dose of below 3 ml/kg.ml/kg.

• The Journal of Internal Korean Medicine
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• v.15 no.1
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• pp.80-98
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• 1994

According to the original documents, Sagungsan is considered as an effective drug for controlling the hypertensive epistaxis induced by tension of autonomic nerve and it's hyperfunction. The present experiment was designed to understand the effect of Sagungsan extract on the hemostatic action, intracranial pressure, blood pressure and cardiovascular system in experimental animals. And thus the bleeding time, prothrombin time, capillary dilation, blood pressure, Intracranial pressure, and enzymatic analysis of the ATPase activities were studied. The result obtained here were as followings: 1. Sagungsan water extract reduced the bleeding time in mouse, and prolonged the prothrombin time in rabbits. 2. The drug extract increased the tail volume by capillary dilation in rats. 3. The drug extract inhibited the increase of intracranial pressure and arterial blood pressure in rabbits. 4. At the early time, the increase of arterial blood pressure by the drug extract significantly inhibited by pretreated atropin and regitine in rabbits. 5. The drug extract relaxed the smooth muscle by stimulating the Mg2+-Ca2+-ATPase activities of gastric sarcoplasmic reticulum isolated from rabbit stomach. 6. The drug extract stimulated the heart contraction by inhibiting the $Mg^{2+}-Ca^{2+}-ATPase$ activities of cardiac sarcoplasmic reticulum isolated from rabbit heart. The inhibitory mechanism was reversible and noncompatitive. 7. The drug extract increased the hepatic blood volume by stimulating the hepatic total ATPase activities and hepatic metabolism. 8. The drug extract acted as a tranquilizer by inhibiting the neural Na+-K+-ATPase activity. According to the results, Sagungsan water extract dilated the capillaries, stimulated the heart beat, and thus increased the blood flow with decreasing the intracranial pressure and blood pressure. These effects stanches the epistaxis collectively.

• The Korean Journal of Pain
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• v.10 no.2
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• pp.246-249
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• 1997

Hiccup is defined as an abrupt involuntary contraction of the diaphragm and intercostal muscles with sudden closure of the glottis 35 msec after onset. The term "intractable" is given to those hiccups with a duration ranging from 24 hours to more than 25 years. Short hiccup bouts are mostly associated with gastric distention or alcohol intake, resolved spontaneously or with simple remedies. In contrast, intractable hiccup is a rare but disabling condition which can induce depression, weight loss and sleep deprivation. Although the pathophysiologic mechanisms of hiccup are still poorly understood, wide variety of pathological conditions such as: brain tumor, abdominal tumor, myocardial infarction, renal failure, abdominal surgery etc., can cause intractable hiccup. A 58-year-old male who had suffered from hepatocellular cancer was consulted from medical department due to intractable hiccup. Initial treatment modalities with administrations of metoclopramide and chlorpromazine and nerve block including phrenic nerve block, cervical epidural block and glossopharyngeal nerve block were not effective. Administration of midazolam and baclofen however achieved desirable effect.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.609-616
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• 2017

Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of $Ca^{2+}$-calmodulin using the activities of 20 kDa myosin light chain ($MLC_{20}$) phosphorylation and myosin $Mg^{2+}$-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low $Ca^{2+}$, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high $Ca^{2+}$, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of $MLC_{20}$ and $Mg^{2+}$-ATPase activities of $Ca^{2+}$- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.

• The Korean Journal of Physiology
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• v.21 no.2
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• pp.241-257
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• 1987

The effects of external $Ca^{2+}$ and $Ca^{2+}-antagonists$ on the spontaneous contractions and electrical activities were investigated in guinea-pig stomach in order to clarify the mechanism for the generation of slow waves. Electrical responses of circular smooth muscle cells were recorded using glass capillary microelectrodes filled with 3 M KCl. 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) The amplitude of spontaneous contractions was maximal at around 2-4 mM $Ca^{2+}$, whereas their frequency was inversely related with external $Ca^{2+}$ within the range of 0.5 to 16 mM $Ca^{2+}$. 2) Verapamil suppressed the amplitude of spontaneous contraction in a dose-dependent manner, while the frequency of spontaneous contractions was almost not changed over the whole concentration of verapamil $(0.01{\sim}5\;mg/l)$. 3) Manganese increased both the amplitude and the frequency of spontaneous contractions dose-dependently in low $Mn^{2+}$ (below 0.05 mM $Mn^{2+}$), while their amplitude and frequency were decreased in high $Mn^{2+}$ (above 0.1 mM $Mn^{2+}$). 4) The ampltude and maximum rate of rise of slow waves were incrased in high $Ca^{2+}$ solution. In $Ca^{2+}-free$ solution, the spontaneous contractions recorded simultaneously with slow waves ceased and tonic contraction ($Ca^{2+}-free$ contracture) was developed in parallel with membrane depolarization and the disappearance of slow waves. 5) Verapamil (1 mg/1) decreased the amplitude and maximum rate of rise of slow waves and it depolarized the membrane by about 6 mV, whereas the frequency of slow waves was not affected by verapamil. 6) Manganese showed different characteristic effects between low and high $Mn^{2+}$ on the slow waves: In low $Mn^{2+}$ (0.05 mM $Mn^{2+}$), the initial rapid increases and the subsequent gradual decreases in three parameters of slow waves (amplitude, rate of rise, and frequency of slow waves) till a new steady state were observed. However, in high $Mn^{2+}$ (0.5 mM $Mn^{2+}$) slow waves disappeared and membrane was depolarized. From the above results, the following conclusions could be made: 1) $Ca^{2+}$ is necessary for a generation of the slow waves, even though it is small amount. 2) Verapamil suppresses the spontaneous contractions of gastric antral strip by the decreases in amplitude and maximum rate of rise of slow waves, while this drug does not block the $Ca^{2+}-channel$ involved in the generation of slow waves. 3) Manganese has dual actions on the $Ca^{2+}-channels$; the $Ca^{2+}-channel$ involved in the generation of slow waves (or Na-Ca exchange system) or the channel for the generation of spike potentials are stimulated by a low concentration of $Mn^{2+}$, while both the $Ca^{2+}$. Channels are blocked by high concentration of $Mn^{2+}$.

• The Korean Journal of Physiology
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• v.28 no.1
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• pp.37-50
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• 1994

Synthetic potassium channel openers (KCOs) are agents capable of opening K-channels in excitable cells. These agents are known to have their maximal potency in the smooth muscle tissue, especially in the vascular smooth muscle. Much attention has been focused on the type of K-channel that is responsible for mediating the effects of KCOs. As the KCO-induced changes are antagonized by glibenclamide, an $K_{ATP}$ (ATP-sensitive K-channel) blocker in the pancreatic ${\beta}-cell,\;K_{ATP}$ was suggested to be the channel responsible. However, there also are many results in favor of other types of K-channel $$(maxi-K,\;small\;conductance\;K_{Ca,}\; SK_{ATP}) mediating the effects of KCOs. Effects of lemakalim, (-)enantiomer of cromakalim (BRL 34915), on the spontaneous contractions and slow waves, were investigated in the antral circular muscle of the guinea-pig stomach. Membrane currents and the effects on membrane currents and single channel activities were also measured in single smooth muscle cells and excised membrane patches by using the patch clamp method. Lemakalim induced hyperpolarization and inhibited spontaneous contractions in a dose-dependent manner. These effects were blocked by glibenclamide and low concentrations of tetraethyl ammonium (< mM). Glibenclamide blocked the effect of lemakalim on the membrane potential and slow waves. The mechanoinhibitory effect of lemakalim was blocked by pretreatment with glibenclamide. In a whole ceIl patch clamp condition, lemakalim largely increased outward K currents. These outward K currents were blocked by TEA, glibenclamide and a high concentration of intracelIular EGTA (10 mM). Volatage-gated Ca currents were not affected by lemakalim. In inside-out patch clamp experiments, lemakalim increased the opening frequency of the large conductance $Ca^{2+}-activated$ K channels $(BK_{Ca},\;Maxi-K).$ From these results, it is suggested that lemakalim induces hyperpolarization by opening K-channels which are sensitive to internal Ca and such a hyperpolarization leads to the inhibition of the spontaneous contraction.