• 대한한방내과학회지
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• 제42권4호
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• pp.707-717
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• 2021

Objectives: The aim of this study was to introduce the normalization effects of stimulation of both ST36 and CV11, 12, 13 meridian points on the abnormal gastric myoelectrical activity in two cases of functional dyspeptic patients with gastric dysmotility. Methods: Gastric myoelectrical activity was recorded by electrogastrography every two weeks until their gastric myoelectrical activity finally reached the normality. Dominant frequency of gastric slow waves in the fasting and postprandial periods and a dominant power ratio were obtained on each occasion. Patients were treated three times each day: 9 am, 1 pm, and 7 pm. The first treatment consisted of manual and immersion stimulation on all used meridian points for 20 min. In the second and third treatments, electrical stimulation of both ST36 was added. It was conducted for 20 min at a strength intensity of 1.2 times the pain threshold at a frequency of 3 Hz. Results: Stimulation of the above meridian points normalized abnormal gastric myoelectrical activity. The time taken to return from abnormal gastric myoelectrical activity to normal was 16-19 weeks. Conclusion: Stimulation of both ST36 and CV11, 12, 13 meridian points normalized the abnormal gastric myoelectrical activity in the functional dyspepsia of gastric dysmotility.

• The Korean Journal of Physiology and Pharmacology
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• 제2권3호
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• pp.361-368
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• 1998

The spontaneous contractions of gastric smooth muscles are regulated by slow waves, which are modulated by both nervous system and humoral agents. This study was designed to examine the effects of prostaglandin $E_2$ ($PGE_2$) on the contractile and electrical activities of antral smooth muscles in guinea-pig stomach, using an intracellular recording technique. To elucidate the underlying mechanism for its effect on contractility, ionic currents were also measured using a whole-cell patch clamp method. The basal tone by $PGE_2$ was variable, whereas the magnitude of phasic contractions was reduced ($19.0{\pm}2.1%$, n=19). The resting membrane potentials were hyperpolarized ($-4.4{\pm}0.5%$ mV, n=10), and plateau potentials were lowered ($-2.9{\pm}0.5%$ mV, n=10). In most cases, however, the initial peak potentials of slow waves were depolarized more by $PGE_2$ than those of control. The frequency of the slows wave was increased from $5.7{\pm}0.2$ cycles/min to $6.5{\pm}0.2$ (n=22). Voltage-operated $Ca^{2+}$ currents were decreased by $PGE_2$ (n=5). Voltage-operated $K^+$ currents, both Ca-dependent and Ca-independent, were increased (n=5). These results suggest that $PGE_2$ plays an important role in the modulation of gastric smooth muscle activities, and its inhibitory effects on the contractility and activities of slow waves are resulted from both decrease of $Ca^{2+}$ currents and increase of $K^+$ currents.

• The Korean Journal of Physiology and Pharmacology
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• 제3권2호
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• pp.119-125
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• 1999

Mammalian gastric smooth muscles generate spontaneous rhythmic contractions which are associated with slow oscillatory potentials (slow waves) and spike potentials. Spike potentials are blocked by organic $Ca^{2+}-antagonists,$ indicating that these result from the activation of L-type $Ca^{2+}-channel.$ However, the cellular mechanisms underlying the generation of slow wave remain unclear. Slow waves are insensitive to $Ca^{2+}-antagonists$ but are blocked by metabolic inhibitors or low temperature. Recently it has been suggested that Interstitial Cells of Cajal (ICC) serve as pacemaker cells and a slow wave reflects the coordinated behavior of both ICC and smooth muscle cells. Small segments of circular smooth muscle isolated from antrum of the guinea-pig stomach generated two types of electrical events; irregular small amplitude (1 to 7 mV) of transient depolarization and larger amplitude (20 to 30 mV) of slow depolarization (regenerative potential). Transient depolarization occurred irregularly and membrane depolarization increased their frequency. Regenerative potentials were generated rhythmically and appeared to result from summed transient depolarizations. Spike potentials, sensitive to nifedipine, were generated on the peaks of regenerative potentials. Depolarization of the membrane evoked regenerative potentials with long latencies (1 to 2 s). These potentials had long partial refractory periods (15 to 20 s). They were inhibited by low concentrations of caffeine, perhaps reflecting either depletion of $Ca^{2+}$ from SR or inhibition of InsP3 receptors, by buffering $Ca^{2+}$ to low levels with BAPTA or by depleting $Ca^{2+}$ from SR with CPA. They persisted in the presence of $Ca^{2+}-sensitive$ $Cl^--channel$ blockers, niflumic acid and DIDS or $Co^{2+},$ a non selective $Ca^{2+}-channel$ blocker. These results suggest that spontaneous activity of gastric smooth muscle results from $Ca^{2+}$ release from SR, followed by activation of $Ca^{2+}-dependent$ ion channels other than $Cl^-$ channels, with the release of $Ca^{2+}$ from SR being triggered by membrane depolarization.

• The Korean Journal of Physiology
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• 제21권2호
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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 and Pharmacology
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• 제4권3호
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• pp.227-234
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• 2000

Many reports suggest that neurotensin (NT) in the gastrointestinal tract may play a possible role as a neurotransmitter, a circulating hormone, or a modulator of motor activity. NT exerts various actions in the intestine; it produces contractile and relaxant responses in intestinal smooth muscle. This study was designed to investigate the effect of NT on motility of antral circular muscle strips in guinea-pig stomach. To assess the role of $Ca^{2+}$ influx in underlying mechanism, slow waves were simultaneously recorded with spontaneous contractions using conventional intracellular microelectrode technique. At the concentration of $10^{-7}$ M, where NT showed maximum response, NT enhanced the magnitude $(863{\pm}198%,\;mean\;SEM,\;n=13)$ and the frequency $(154{\pm}10.3%,\;n=11)$ of spontaneous contractions. NT evoked a slight hyperpolarization of membrane potential, tall and steep slow waves with abortive spikes $(278{\pm}50%,\;n=4).$ These effects were not affected by atropine $(2\;{\mu}M),$ guanethidine $(2\;{\mu}M)$ and tetrodotoxin (0.2μM). NT-induced contractile responses were abolished in $Ca^{2+}-free$ solution and reduced greatly to near abolition by $10\;{\mu}M$ of verapamil or 0.2 mM of $CdCl_2.$ Verapamil attenuated the effects of NT on frequency and amplitude of the slow waves. Taken together, these results indicate that NT enhances contractility in guinea-pig gastric antral circular muscle and $Ca^{2+}$ influx through the voltage-operated $Ca^{2+}$ channel appears to play an important role in the NT-induced contractile mechanism.

• 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 $Ca^{2+}\;-dependent\;K^+\;channels$.

• The Korean Journal of Physiology
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• 제24권1호
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• pp.39-49
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• 1990

bombesin의 생물학적 활성중 하나는 위장관의 평활근을 수축시키는 작용이다. 그러므로, 본 실험에서는 bombesin이 위장관의 운동성과 관계가 깊은 평활근의 전기적 활동에 미치는 영향과 신경기전을 밝히고자 하였다. 고양이 60마리로부터 urethane마취하에 위를 적출한 다음 대만 쪽에서 체부와 유문부가 포함된 평활근 절편을 얻었으며 또한 체부에서 윤상근 절편을 얻었다. 평활근 절편을 Krebs-Ringer 용액으로 채워진 기록용기에 넣고 Ag-AgCl전극을 사용하여 체부와 유문부에서 서파를 기록하는 한편 윤상근 절편의 자발적 수축을 기록하였다. 기록용기 속의 용액에는 5% $Co_{2}$를 내포한 $O_{2}$를 계속 공급하였으며, 용액의 온도는 $36^{\circ}C$가 유지되도록 하였다. 기록용기 속에서 1시간 동안 안정시킨 다음 서파빈도와 수축빈도가 일정하여지면 bombesin과 그 유도체, substance P와 그 유도체 그리고 몇가지 종류의 신경차단제를 각각 투여하여 다음과 같은 결과를 얻었다. 1) bombesin은 $10^{-9}\;M$에서부터 $3\;{\times}\;10^{-8}\;M$ 사이의 농도에서 서파빈도와 수축빈도를 농도-의존적으로 증가시켰다. 2) bombesin 유도체인 $D-leu^{13}-{\psi}\;(CH_{2}NH)-D-leu^{14}-bombesin$은 서파빈도를 증가시키는 bombesin의 작용을 억제하였다. 3) 서파빈도를 증가시키는 bombesin의 작용에 대하여 tetrodotoxin과 hexamethonium은 억제적으로 작용하였으나 atropine, phentolamine 그리고 propranolol은 이렇다할 영향을 비치지 않았다. 4) 서파빈도를 증가시키는 bombesin의 작용에 대하여 substance P 유도체인 $D-pro^{2}-D-trp^{7,9}-substance\;P$는 억제적으로 작용하였다. 5) sunstance P 자체는 서파빈도에는 영향을 미치지 않았다. 이상의 결과로 보아 (1) bombesin은 적출한 고양이 위 평활근의 서파빈도와 체부 윤상근의 수축빈도를 증가시키며, (2) bombesin은 신경-근 연접에서 acetylcholine이나 noradrenalin을 신경전달물질로 사용하지 않는 내원성 신경을 거쳐 서파빈도를 증가시키는 것으로 생각된다. (3) 그러나, bombesin이 서파의 발생빈도를 증가시키는 과정에 substance P를 신경전달물질로 사용하는 신경이 개재하는 것 같지는 않았다.

• 대한한방내과학회지
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• 제25권4호
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• pp.158-166
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• 2004

Background & Object : The aim of this study was to investigate the usefulness of electrogastrography in the diagnosis field of traditional medicine through a study of the relationship between gastric motility and health condition based on oriental medicine diagnostic theory in functional dyspepsia. Method : 86 patients (male 27, female 59) with functional dyspepsia and 10 healthy control subjects (male 5, female 5) were involved in the investigation. The disease information of functional dyspepsia (based on Rome criteria II) was used for dyspeptic index and scores were obtained from the comprehensive diagnosis of Qui, Xue, Shui was applied as index for health condition, those were all investigated by questionnaire. Gastric motility were recorded and analyzed using electrogastrography in fasting and postprandial period. Results : The total score of comprehensive diagnosis of Qui Xue Shui was influenced by the number of functional dyspepsia symptoms (p=0.026). In terms of electrogastrographical parameters, both postpranial normal slow waves regularity(p=0.003) and power ratio (p=0.001) in the patients had the statistical significance and they showed an incremental inverse correlation with the number of symptoms. Dominant frequency and fasting normal slow waves regularity ratio had no statistical significance. Conclusion : Results suggest that electrogastrography is useful in evaluating the health condition of patient by comprehensive diagnosis of Qui Xue Sui.

• Molecules and Cells
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• 제20권3호
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• pp.435-441
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• 2005

Classical transient receptor potential channels (TRPCs) are thought to be candidates for the nonselective cation channels (NSCCs) involved in pacemaker activity and its neuromodulation in murine stomach smooth muscle. We aimed to determine the role of TRPC4 in the formation of NSCCs and in the generation of slow waves. At a holding potential of -60 mV, $50{\mu}M$ carbachol (CCh) induced $I_{NSCC}$ of amplitude [$500.8{\pm}161.8pA$ (n = 8)] at -60 mV in mouse gastric smooth muscle cells. We investigated the effects of commercially available antibodies to TRPC4 on recombinant TRPC4 expressed in HEK cells and CCh-induced NSCCs in gastric smooth muscle cells. TRPC4 currents in HEK cells were reduced from $1525.6{\pm}414.4pA$ (n = 8) to $146.4{\pm}83.3pA$ (n = 10) by anti-TRPC4 antibody and $I_{NSCC}$ amplitudes were reduced from $230.9{\pm}36.3pA$ (n = 15) to $49.8{\pm}11.8pA$ (n = 9). Furthermore, $I_{NSCC}$ in the gastric smooth muscle cells of TRPC4 knockout mice was only $34.4{\pm}10.4pA$ (n = 8) at -60 mV. However, slow waves were still present in the knockout mice. Our data suggest that TRPC4 is an essential component of the NSCC activated by muscarinic stimulation in the murine stomach.

• 대한한방내과학회지
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• 제29권1호
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• pp.189-199
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• 2008

Background & Objective : Jichul-hwan(JCH) has been used for the treatment of functional dyspepsia, regarded as a gastric dysmotility disease. We investigated the effects of JCH on gastric motility and its mechanisms of action in rats. Methods : The gastric wall was injured by tracting a part of stomach body in rats. Gastric emptying was measured after administration of normal saline(NS) or JCH in normal rats and gastric wall injured rats. To evaluate the mechanism of JCH under delayed gastric emptying conditions, normal rats were treated with atropine sulfate(1mg/kg, s.c.), quinpirole HCl(0.3mg/kgg, i.p.), $NAME(N^{G}-nitro-L-arginine$ methyl ester, 75mg/kg s.c.) and cisplatin(10mg/kg, i.p.). The gastric slow waves were measured for 30 minutes before and after administration of each solution(NS, JCH). Results : JCH 110.1mg/kg improved gastric emptying for 2 hrs(p=0.014). JCH 110.1mg/kg improved gastric emptying in the gastric wall injured rats(p=0.001). Under the delayed gastric emptying, JCH 110.1mg/kg improved gastric emptying in the group treated with atropine $sulfate(1.83{\pm}0.96$ vs $8.43{\pm}8.46$, p=0.003), but aggravated it with quinpirole $HCl(4.7{\pm}2.9$ vs $1.61{\pm}2.09$, p=0.021). Administration JCH 110.1mg/kg increased EGG power in rats. Conclusions : JCH stimulates gastric motility through the cholinergic pathway, so we expect that it would be effective in the treatment of dysmotility-like functional dyspepsia with low activity of vagus nerve.