• The Korean Journal of Pharmacology
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• v.28 no.1
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• pp.81-89
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• 1992

Enuresis is a common voiding disorder among children. There are several therapeutic regimens for the disorder available today; behavioral therapies, psychotherapy, bladder training, sleep interruption, hypnosis and drug therapy. Recently, the efficacy of drug therapy has been acknowledged, particularly of antidepressants. Among the tricyclic antidepressants, imipramine is most frequently employed for the treatment of enuresis. Present study was undertaken to investigate the mechanism of imipramine on the contractility of urinary bladder in relation to the calcium modulation using isolated strips of rat detrusor urinae. 1. The electric fileld stimulation-induced contraction was abolished by imipramine, but partially inhibited by atropine. 2. Imipramine reduced the basal tone and diminished the phasic activity of detrusor muscle concentration-dependently, which was similar to that of diltiazem, a calcium channel blocker. 3. Imipramine suppressed the maximal responses and shifted the concentration-response curves of bethanechol and ATP to right. 4. Imipramine inhibited the calcium-induced recovery of tension in calcium-free physiologic salt solution (PSS) with a mode of action similar to that of diltizaem. 5. A23187, a calcium ionophore recovered the basal tone which had been reduced by imipramine in normal PSS. 6. In calcium-free PSS, A23187 could recover the abolished basal tone with the pretreatment of imipramine, but it exerted a partial recovery with the pretreatment of TMB-8, an inhibitor of intracellular calcium release. Based on these results, it is suggested that the inhibitory action of imipramine on the detrusor muscle exerted in part by blockade of the muscarinic and purinergic receptors, and interference with the influx of extracellular calcium, but not with the release of intracellular stored calcium, is involved in its mechanism of action.

• The Korean Journal of Physiology and Pharmacology
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• v.18 no.6
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• pp.517-524
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• 2014

Phasic and tonic ${\gamma}$-aminobutyric acidA ($GABA_A$) receptor-mediated inhibition critically regulate neuronal information processing. As these two inhibitory modalities have distinctive features in their receptor composition, subcellular localization of receptors, and the timing of receptor activation, it has been thought that they might exert distinct roles, if not completely separable, in the regulation of neuronal function. Inhibition should be maintained and regulated depending on changes in network activity, since maintenance of excitation-inhibition balance is essential for proper functioning of the nervous system. In the present study, we investigated how phasic and tonic inhibition are maintained and regulated by different signaling cascades. Inhibitory postsynaptic currents were measured as either electrically evoked events or spontaneous events to investigate regulation of phasic inhibition in layer 2/3 pyramidal neurons of the rat visual cortex. Tonic inhibition was assessed as changes in holding currents by the application of the $GABA_A$ receptor blocker bicuculline. Basal tone of phasic inhibition was maintained by intracellular $Ca^{2+}$ and $Ca^{2+}$/calmodulin-dependent protein kinase II (CaMKII). However, maintenance of tonic inhibition relied on protein kinase A activity. Depolarization of membrane potential (5 min of 0 mV holding) potentiated phasic inhibition via $Ca^{2+}$ and CaMKII but tonic inhibition was not affected. Thus, phasic and tonic inhibition seem to be independently maintained and regulated by different signaling cascades in the same cell. These results suggest that neuromodulatory signals might differentially regulate phasic and tonic inhibition in response to changes in brain states.

• Korean Journal of Oriental Medicine
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• v.3 no.1
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• pp.215-228
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• 1997

Extrapyramidal movement disorders are divided descriptively into hypokinesias(such as parkinsonism), characterized by poverty and slowness of movement : hyperkinesias(such as chorea, athetosis, dystonia, ballism, etc.), manifested by abnormal involuntary movement. Chorea refers to widespread arrythythmic movements of a forcible, rapid, jerky, restless type Choreic movements are noted for their irregularity and variability. They are generally continuous, may be simple or quite elaborate, and affect any part of the body. Dystonla refers to abnormally increased muscular tone that causes fixed abnormal postures. Some patients with dystonia also have shifting postures, resulting from irregular, forceful twisting movement that affect trunk and produce bizarre, grotesque movements and positions of the body. The most frequent and familiar type of focal dystonia is spasmodic torticollis. It consists of an involuntary turning of the head to one side - intermittent at first, then gradually worsening to the point of being more or loss continuous. The combination of blepharospasm and oromandibular dystonia is sometimes refered to as Meige's syndrome. We report two patients with dystonia and chorea in cerebral infarction at basal ganglia. We have experienced good improvement by the oriental medicine and acupuncture treatment.'rho acupuncture points of LI 4, ST 36, TE 3, GB 34, GB 41, LR 3, GB 39 were used. The therapies of herb-medicine were treated by Zibu-Ganshen(滋補肝腎), Huoxue-Xifeng-Tongluo(活血息風通絡).

• Archives of Pharmacal Research
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• v.12 no.2
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• pp.128-134
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• 1989

$Na^+-Ca^{2+}$ exchange process in sarcolemmal vesicles isolated from mesenteric arteries of Wistar-Kyoto normotensive(WKY) and spontaneously hypertensive rats(SHR) was investigated. The sarcolemmal fractions isolated after homogenization and sucrose density gradient centrifugation were enriched with 5'-nucleotidase and ouabain sensitive, $K^+-dependent$ phosphatase activities. When the vesicles were loaded with $Na^+$, a time dependent $Ca^{2+}$ uptake was observed. However, very little $Ca^{2+}$ uptake was observed when the vesicles were loaded with $K^+$, or $Ca^{2+}$ uptake of the $Na^+-loaded$ vesicles was carried out in high sodium medium so that there was no sodium gradient. When the vesicles loaded with $Ca^{2+}$ by $Na^+-Ca^{2+}$ exchange were diluted into potassium medium containing EGTA, $Ca^{2+}$ was rapidly released from the vesicles. $Na^+-dependent\;Ca^{2+}$ uptake was increased in SHR compared to WKY, but passive efflux of preaccumulated $Ca^{2+}$ from the vesicles was decreased in SHR. The data indicate that the membrane vesicles of rat mesenteric arteries exhibit $Na^+-Ca^{2+}$ exchange activity. It is also suggested that changes of this process in vascular smooth muscle cell membrane of SHR may be involved in higher intracellular $Ca^{2+}$ concentration and higher basal tone in SHR.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.1
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• pp.99-106
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• 2017

Obesity is a critical risk factor for the hypertension. Although angiotensin II (Ang II) in obese individuals is known to be upregulated in obesity-induced hypertension, direct evidence that explains the underlying mechanism for increased vascular tone and consequent increase in blood pressure (BP) is largely unknown. The purpose of this study is to investigate the novel mechanism underlying Ang II-induced hyper-contractility and hypertension in obese rats. Eight-week old male Sprague-Dawley rats were fed with 60% fat diet or normal diet for 4 months. Body weight, plasma lipid profile, plasma Ang II level, BP, Ang II-induced vascular contraction, and expression of regulatory proteins modulating vascular contraction with/without Ang II stimulation were measured. As a result, high fat diet (HFD) accelerated age-dependent body weight gaining along with increased plasma Ang II concentration. It also increased BP and Ang II-induced aortic contraction. Basal expression of p-CPI-17 and myosin light chain (MLC) kinase was increased by HFD along with increased phosphorylation of MLC. Ang II-induced phosphorylation of CPI-17 and MLC were also higher in HFD group than control group. In conclusion HFD-induced hypertension is through at least in part by increased vascular contractility via increased expression and activation of contractile proteins and subsequent MLC phosphorylation induced by increased Ang II.

• YAKHAK HOEJI
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• v.53 no.3
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• pp.156-160
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• 2009

The present study was undertaken to determine whether transgelin participates in the regulation of vascular smooth muscle contraction and, if so, to investigate the mechanism. By PCR homology cloning, the cDNA sequence of ferret transgelin was determined and phosphorothioate antisense and random oligonucleotides were synthesized and introduced into strips of ferret aorta by a chemical loading procedure. Treatment of ferret aorta with transgelin antisense oligonucleotides resulted in a significant decrease in protein levels of transgelin to sham- or random sequence-loaded muscles, but no change in the protein levels of actin. Contraction in response to a phorbol ester was significantly decreased in antisense-treated muscles compared to sham- or random sequence-loaded controls. Neither basal intrinsic tone nor the contraction in response to phenylephrine was significantly affected by the antisense treatment. The data indicate that transgelin plays a significant role in the regulation of contraction and suggest that in a tonically active smooth muscle transgelin may function as a signalling protein to facilitate PKC or ERK-dependent signalling rather than thick filament regulation including $Ca^{2+}$ or calmodulin dependent regulation of myosin light chain kinase.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.6
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• pp.715-724
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• 1998

Frequency-force relationships (FFR) were studied in electrically field stimulated rat left atria (LA) by reducing the stimulation frequency from resting 3 Hz to test frequencies (0.1-1 Hz) for 5 minutes. The twitch amplitudes of LA elicited the typical negative staircases with 3-phased changes: the initial rapid increase, the second decrease and the following plateau at test frequencies. Verapamil $(3{\times}10^{-5}\;M)$ pretreatment elicited frequency-dependent suppression of the twitch amplitudes, exaggerating the negative staircase. Monensin pretreatment enhanced not the peak but the plateau amplitudes in a concentration-dependent manner. When the $Na^+-Ca^{2+}$ exchange was blocked by $Na^+\;and\;Ca^{2+}$ depletion in the Krebs Hensleit buffer (0 $Na^+-0\;Ca^{2+}$ KHB), the twitch amplitudes increased in a frequency-dependent manner, changing the negtive staircase into the positve one. Meanwhile, the 0 $Na^+-0\;Ca^{2+}$ KHB applicationinduced enhancement was strongly suppressed by caffeine (5 mM) pretreatment. Only dibucaine among the local anesthetics increased the basal tone during frequency reduciton. There were no differences in $^{45}Ca$ uptakes between 0.3 Hz and 3 Hz stimulation except at 1 min when it was significantly low at 0.3 Hz than 3 Hz, illustrating net $Ca^{2+}$ losses. Monensin pretreatment enhanced the rate of this $Ca^{2+}$ loss. Taken together, it is concluded that $Na^+-Ca^{2+}$ exchange extrudes more SR released $Ca^{2+}$ out of the cell in proportion to the frequency, resulting in the negative rate staircase in the rat LA.

• Biomolecules & Therapeutics
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• v.1 no.2
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• pp.211-219
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• 1993

The general and some pharmacological actions of DWP 302 were investigated in animals and the following results were obtained. In central nervous system, DWP 302 had no effects on the pentobarbital induced anaesthesia, locomotor activity, rotarod test, traction test, analgesic action in the mice and body temperature in the rat. DWP 302 showed no depressive action on the convulsion induced by strychnine and electronic shock. From these results, DWP 302 was considered to have no or little pharmacological effect on the central nervous system. Furthermore, DWP 302 had no influences on the normal blood pressure and heart rate. In the isolated ileum of guinea pig, DWP 302 showed neither contractive nor relaxing effects against the acetylcholine ($10^{-6}g/mι$), histamine ($10^{-6}g/mι$) and $BaCl_2$ ($10^{-4}g/mι$) at a concentration of $1.9{\times}10^{-4}g/mι$ in bath. But it caused a slight increase in basal tone at a concentration of $6.3{\times}10^{-4}g/mι$ and this effect was inhibited by atropine $10^{-7}g/mι.$ In the isolated trachea and vas deference, DWP 302 showed no effect on the contractions produced by histamine and norepinephrine, respectively. And DWP 302 showed no effect on the contractions produced by acetylcholine and oxytocin in the isolated nonpregnant rat uterus. DWP 302 had no effect on bile excretion, urine volume, pH and gastrointestinal motility, But, DWP 302 showed a significant inhibitory effect on gastric secretion in the rat.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.5
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• pp.573-580
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• 1998

The study aims to identify the mechanism (s) underlying the altered vasodilatory responses of the pial artery of spontaneously hypertensive rats (SHR) under a hypothesis that calcitonin gene-related peptide (CGRP) exerts a modulator role in the autoregulation of cerebral blood flow (CBF). The animals were divided into four groups: 1) Sprague-Dawley rats (SDR), 2) Wistar rats (WR), 3) SHR with high blood pressure $(BP{\ge}150\;mmHg),$ and 4) SHR with normotensive BP $({\le}150\;mmHg).$ The lower limit of CBF autoregulation in SHR shifted to a higher BP $(82.8{\pm}9.3\'mmHg,\;P<0.05)$ than that in SDR $(58.9{\pm}5.7\;mmHg)$. In SHR, whether the BP levels were high or normotensive, the vasodilator responses to a stepwise hypotension were significantly attenuated unlike with SDR and WR. When artificial cerebrospinal fluid (CSF) containing capsaicin $(3{\times}10^{-7}\;M)$ was suffused over the cortical surface, a transient increase in pial arterial diameter was observed in the SHR with high or normotensive BP. In contrast, SDR and WR showed a large increase in diameter, and the increase was sustained for over 10 minutes. In line with these results, the basal releases of CGRP-like immunoreactivity (CGRP-LI) in the isolated pial arteries from SHR with high and normotensive BP were $12.5{\pm}1.4\;and\;9.8{\pm}2.8\;fmole/mm^2/60\;min\;(P<0.05)$, while those from SDR and WR were $25.5{\pm}3.1\;and\;24.6{\pm}3.1\;fmole/mm^2/60\;min,$ respectively. The isolated basilar arteries showed similar results to those of the pial arteries in SHR. Thus, it is summarized that, in the SHR, the reduced autoregulatory vasodilator responses to stepwise hypotension and capsaicin may be, in part, ascribed to the decreased release of CGRP from the perivascular sensory nerve fibers of the pial arteries, and that altered vasomotor activity in SHR may not be related with the hypertensive tone.

• The Korean Journal of Physiology and Pharmacology
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• v.21 no.6
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• pp.617-623
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• 2017

The vascular actions and mechanisms of taurine were investigated in the isolated human radial artery (RA). RA rings were suspended in isolated organ baths and tension was recorded isometrically. First, a precontraction was achieved by adding potassium chloride (KCl, 45 mM) or serotonin (5-hydroxytryptamine, 5-HT, $30{\mu}M$) to organ baths. When the precontractions were stable, taurine (20, 40, 80 mM) was added cumulatively. Antagonistic effect of taurine on calcium chloride ($10{\mu}M$ to 10 mM) -induced contractions was investigated. Taurine-induced relaxations were also tested in the presence of the $K^+$ channel inhibitors tetraethylammonium (1 mM), glibenclamide ($10{\mu}M$) and 4-aminopyridine (1 mM). Taurine did not affect the basal tone but inhibited the contraction induced by 5-HT and KCl. Calcium chloride-induced contractions were significantly inhibited in the presence of taurine (20, 40, 80 mM) (p<0.05). The relaxation to taurine was inhibited by tetraethylammonium (p<0.05). However, glibenclamide and 4-aminopyridine did not affect taurine -induced relaxations. Present experiments show that taurine inhibits 5-HT and KCl -induced contractions in RA, and suggest that large conductance $Ca^{2+}$-activated $K^+$ channels may be involved in taurine -induced relaxation of RA.