• The Journal of Internal Korean Medicine
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• v.34 no.2
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• pp.147-154
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• 2013

Objectives : The aims of this study was to find out whether Jichul-hwan (JCH) extract has an effect on gastric contractility in conscious rats by using a force transducer implanted in the body of the stomach. Methods : The force transducer (model: F-081S, Starmedical, JAPAN) was implanted to the exterior wall of the stomach body in rats. The gastric contractility was measured 30 minutes before and after administration of JCH (110.1 mg/kg). The control group was administrated with normal saline instead of JCH to compare the effect of JCH. The gastric contractility of the control group (normal saline: NS) was also measured 30 minutes before and after administration of NS. Results : The ratio of gastric contractility between before and after medication by JCH was $1.707{\pm}0.731$, and with NS was $0.701{\pm}0.541$. The gastric motility increased by JCH was significantly higher than NS. Conclusions : JCH extract increases gastric contractility in conscious rats. We could expect that this drug would be effective in the treatment of functional dyspepsia or post-surgical gastroparesis.

• The Journal of Internal Korean Medicine
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• v.35 no.4
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• pp.439-447
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• 2014

Objectives: The aim of this study was to investigate whether 1) variation of bowel sounds recorded stably through an electronic stethoscope in a sound insulation box can be related with that of gastric contraction and 2) if they are thus useful tool in the measurement of the gastric contractility in awake rats or not. Methods: Electrical potentials of both electronic stethoscope of bowel sound and force transducer were recorded simultaneously and continuously in the sound insulation box for the starting 30 min of basal state, and then 30 min of 0.2 ml normal saline administration, finally 30 min of 0.2 ml mosapride citrate solution (100 mg/Kg) in rats. Each motility index of normal saline or mosapride citrate treatment was presented with ratio against the basal state by using integrated electrical potentials. Results: A pattern of significance of gastric contractility between bowel sound and force transducer was showed analogously. Conclusions: The amplitude of bowel sounds recorded by the electronic stethoscope related with the intensity of gastric contractions. This confirms that a sound insulation box and electronic stethoscope are useful tools in the measurement of the gastric contractility of awake rats.

• The Journal of Internal Korean Medicine
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• v.31 no.2
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• pp.212-223
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• 2010

Objectives : The aims of this study were to evaluate whether gastric contractility could be measured by bowel sound of rats, and whether gastrointestinal side effect of any herbal restoratives would be related with their inhibition of gastric contraction. Methods : Streptozotocin (STZ)-induced diabetic rats were used as a gastric hypocontraction model. At the time of 6 weeks after induction of diabetes, 2mL of normal saline (NS) and 2mL of extract solution each containing 125mg/kg of Bojoongikki-tang (BJ), Sipjeondaebo-tang (SJ), Youngkaechulgam-tang (YG) were given to Normal (NR) and diabetic rats (DR), respectively. Bowel sound was recorded for 30 minute in fasting, and 120 minute of their administration. Gastric motility index was serially calculated with the ratio of accumulated potentials of post-administration/fasting state every 10 minutes. Results : Gastric contractility between NR and DR could be significantly distinguished by bowel sound auscultation. BJ had a decreasing effect, SJ had a bidirectional effect, and YG had an increasing effect on gastric contractility measured by bowel sound auscultation. Conclusions : BJ showed the possibility of inhibitory effects on gastric contraction. So, before administration, a gastric motility test should be recommended to prevent possible side effects in patients with gastric hypocontractility.

• The Journal of Internal Korean Medicine
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• v.31 no.4
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• pp.857-869
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• 2010

Objectives : The aim of this study was to evaluate whether rats with non-obstructive antral dilation could be a useful tool resembling functional dyspeptic patients. We also investigated the effect of Bojoongikki-tang (BJ), and Youngkaechulgam-tang (YK) in antral dilated rats. Methods : Non-obstructive antral dilation was performed by first wrapping a non-absorbable rubber ring (D:6mm, W:4mm, T:1mm) around the 1st portion of the duodenum causing pyloric obstruction (PO). After 12 weeks, except for some PO group rats used for the control, the rubber ring was removed by performing another operation. The antral dilated rats (AD) were then divided into three groups, a non-treatment group (AD-NT), and two herbal medicine groups each given an extract solution containing 125 mg/kg of Youngkaechulgam-tang (AD-YK) or Bojoongikki-tang (AD-BJ) for 4 weeks. Then gastric contractility was evaluated by bowel sound measurement, and afterwards the changes of the weight, and morphologic changes of the stomach were evaluated for each group including the normal intact group (NI). Results : Loss of weight and enlargement of the stomach surface area was seen in the PO group. Decrease of gastric motility index was observed in the AD-NT group, while the increased surface area of the stomach was not significantly different from the PO group. Youngkaechulgam-tang seemed to increase gastric contraction, whereas Bojoongikki-tang showed no effect. Weight gain of rats was observed in both the AD-YK and AD-BJ groups, but there seemed to be no change of the dilated stomach surface area. Conclusions : The non-obstructive antral dilated rat seems to be an experimental pathologic model that reflects the gastric dysmotility similar to functional dyspeptic patients with antral dilation. Therefore patients with dysmotility-like dyspepsia with antral function disorders should be treated efficiently. As Youngkaechulgam-tang is shown to increase both gastric contraction and weight in antral dilated rats, it may be used for treating functional dyspepsia. However, Bojoongikki-tang should be used with caution in patients with gastric dysmotility.

• The Korean Journal of Physiology and Pharmacology
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• v.2 no.3
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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
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• v.29 no.2
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• pp.233-241
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• 1995

The nonapeptide bradykinin has been shown to exhibit an array of biological activities including relaxation/contraction of various smooth muscles. In order to investigate the effects of bradykinin on the contractility and the electrical activity of antral circular muscle of guinea-pig stomach, the isometric contraction and membrane potential were recorded. Also, using standard patch clamp technique, the $Ca^{2+}-activated$ K currents were recorded to observe the change in cytosolic $Ca^{2+}$ concentration. $0.4 {\mu}M$ bradykinin induced a triphasic contractile response (transient contraction-transient relaxation-sustained contraction) and this response was unaffected by pretreatment with neural blockers (tetrodotoxin, atropine and guanethidine) or with apamin. Bradykinin induced hyperpolarization of resting membrane potential and enhanced the amplitude of slow waves and spike potentials. The enhancement of spike potentials was blocked by neural blockers. Both the bradykinin-induced contractions and changes in membrane potential were reversed by the selective $B_2$-receptor antagonist $(N{\alpha}-adamantaneacetyl-_{D}-Arg-[Hyp, Thy,_{D}-Phe]-bradykinin)$. In whole-cell patch clamp experiment, we held the membrane potential at -20 mV and spontaneous and transient changes of Ca-activated K currents were recorded. Bradykinin induced a large transient outward current, consistent with a calcium-releasing action of bradykinin front the intracellular calcium pool, because such change was blocked by pretreatment with caffeine. Bradykinin-induced contraction was also blocked by pretreatment with caffeine. From these results, it is suggested that bradykinin induces a calciumrelease and contraction through the $B_{2}$ receptor of guinea-pig gastric smooth muscle. Enhancement of slow wave activity is an indirect action of bradykinin through enteric nerve cells embedded in muscle strip.

• The Korean Journal of Physiology and Pharmacology
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• v.4 no.3
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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 and Pharmacology
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• v.18 no.5
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• pp.425-430
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• 2014

This study was designed to examine the effects of histamine on gastric motility and its specific receptor in the circular smooth muscle of the human gastric corpus. Histamine mainly produced tonic relaxation in a concentration-dependent and reversible manner, although histamine enhanced contractility in a minor portion of tissues tested. Histamine-induced tonic relaxation was nerve-insensitive because pretreatment with nerve blockers cocktail (NBC) did not inhibit relaxation. Additionally, $K^+$ channel blockers, such as tetraethylammonium (TEA), apamin (APA), and glibenclamide (Glib), had no effect. However, $N^G$-nitro-L-arginine methyl ester (L-NAME) and 1H-(1,2,4)oxadiazolo (4,3-A) quinoxalin-1-one (ODQ), an inhibitor of soluble guanylate cyclase (sGC), did inhibit histamine-induced tonic relaxation. In particular, histamine-induced tonic relaxation was converted to tonic contraction by pretreatment with L-NAME. Ranitidine, the $H_2$ receptor blocker, inhibited histamine-induced tonic relaxation. These findings suggest that histamine produced relaxation in circular smooth muscle of human gastric smooth muscle through $H_2$ receptor and NO/sGC pathways.

• 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.

• Toxicological Research
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• v.16 no.3
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• pp.211-219
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• 2000

The therapeutic effect of AS2-006A, a derivative of asiaticoside, has been studied and is being developed as a new wound-healing agent. In the present study, the general pharmacological effects on 1) central nervous system, 2) autonomic nervous system, 3) respiratory system, 4) gastrointestinal system. 5) cardiovascular system. and 6) urinary system were assessed in experimental animals and in in vitro models. 1. In vivo animal study: External applications of the 1 % gel ointment of AS2-006A to rats at the doses of 200. 600 or 2000 mg/kg body weight showed no observable pharmacological effects. The effects on the central nervous system were assessed by observation of behavior, hexobarbital-induced sleeping time, pentetrazole-induced convulsion assay, body temperature measurements, and observations on spontaneous activity and catalepsy. The gel ointment exhibited no effects on the cardiovascular system (i.e. blood pressure and heart rate), renal physiology (i.e. urine volume and electrolytes excretion) and gas-trointestinal physiology (i.e. intestinal charcoal propulsion and gastric mucosal irritation). 2. In vitro experiments: The effects of AS2-006A on the physiology of smooth and cardiac muscles were assessed. Muscle contractions were isotonically and isometrically measured in organ chambers using a physiograph. Cumulative additions of AS2-006A (10$^{-9}$ -10$^{-5}$ M) induced no changes in the tension of isolated guinea pig ileum and tracheal muscles. AS2-006A only slightly increased contractility of rat atrial and papillary muscles at 10$^{-2}$ M, which was not statistically different from control. These data showed that the gel ointment of AS2-006A could be externally applied as a wound-healing agent with no potential side effects.