• 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.21 no.2
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• pp.225-239
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• 1987

The effects of adenosine on the mechanical contractions and electrical activities were investigated in guinea-pig stomach. Spontaneous contractions of the antral region were recorded with force transducer, and the phasic contractions of fundic region were induced by electrical field stimulation. Electrical responses of smocth muscle cells were recored using glass capillary microelectrodes filled with 3M-KCl. Field stimulation was applied transmurally by using a pair of platinum wire (0.5 mm in diameter) placed on both sides of tissue. 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) Adenosine suppressed the spontaneous contractions of antrum in a dose-dependent manner. 2) The inhibitory effect on antral spontaneous contractions was not influenced by the administration of guanethidine $(5{\times}10^{-6}\;M)$ and atropine $10^{-6}\;M$, or in the presence of dipyridamole $10^{-7}\;M$. 3) The phasic contractions of fundus induced by electrical field stimulation, which disappeared rapidly by the addition of tetrodotoxin $(3{\times}10^{-7}\;M)$, were potentiated by adenosine in the presence of guanethidine. 4) Adenosine decreased the amplitude and the maximum rate of rise of slow waves, and the increased amplitude and rate of rise evoked in the high calcium solution or in the presence of TEA were decreased by adenosine. 5) The non-adrenergic, non-cholinergic inhibitory junction potential (IJP) was inhibited by adenosine in the antral region, while the excitatory junction potential (EJP) in the fundic region was potentiated. From the above results, the following conclusions could be made. 1) Adenosine suppresses the spontaneous contractions of antrum strip by the decrease in amplitude and rate of rise of slow waves. 2) The release of neurotransmitter(s) from non-adrenergic, non-cholinergic nerve terminals is inhibited by adenosine.

• The Korean Journal of Pharmacology
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• v.16 no.1 s.26
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• pp.41-50
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• 1980

Chenodeoxycholic acid(CDCA) has been used as a gallstone dissolving agent since 1972. Recently, ursodeoxycholic acid(UDCA) has been reported to be effective in dissolving gallstones. Both bile acids increased bile flow. The increase in bile flow associated with an increase in cholesterol level in bile after CDCA or UDCA infusion was reported. In this study, using the smooth muscle strips of guinea pig and fowl, responses of the cholates were observed. In addition, the influence of adrenergic blocking agents on the response of the strips to cholates was investigated. Also the effects of cholates on cardiac function were examined by using isolated atria of rabbit and heart of anesthetized frog. The results are as follows: 1) All cholates, such as UDCA, CDCA, and CA produced a marked inhibitory effect on the motility in isolated duodenal strip of guinea pig and fowl, however, only UDCA showed the contraction in the isolated esophagus of fowl. These effects of cholates were blocked by propranolol. 2) In isolated guinea pig stomach strip and gall bladder, cholates exhibited a marked inhibitory effect on the motility and the effects due to UDCA and CA were blocked by phenoxybenzamine while CDCA was not affected. 3) The spontaneous and ouabain induced arrhythmia was partially abolished by cholates. However, concomitant administration of cholates with ouabain or epinephrine caused a marked prolongation in occurrence of atrial arrhythmia in comparison with ouabain or epinephrine alone in isolated rabbit atria. 4) In the heart of anesthetized frog, the epinephrine-induced arrhythmia was partially abolished by cholates. The combined treatment with cholates and ouabain or epinephrine produced a marked prolongation in occurrence of the arrhythmia in comparison with, ouabain or epinephrine alone. From the above results, it can be suggested that the effects of cholates on the smooth muscle of duodenum and esophagus are produced in response to adrenergic ${\beta}$-receptor and the effect or gall bladder and stomach is more likely due to the direct effect on the muscle. In addition, cholates exhibit a slight antiarrhythmic effect on heart, therefore, cholates can be classified as a nonselective antiarrhythmic drug, such as propranolol.

• The Korean Journal of Physiology and Pharmacology
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• v.3 no.2
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• pp.165-174
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• 1999

We explore the question of whether adenosine 5'-triphosphate (ATP) acts as an excitatory neurotransmitter in guinea-pig gastric smooth muscle. In an organ bath system, isometric force of the circular smooth muscle of guinea-pig gastric antrum was measured in the presence of atropine and guanethidine. Under electrical field stimulation (EFS) at high frequencies (＞20 Hz), NO-mediated relaxation during EFS was followed by a strong contraction after the cessation of EFS (a 'rebound-contraction'). Exogenous ATP mimicked the rebound-contraction. A known $P_{2Y}-purinoceptor$ antagonist, reactive blue 2 (RB-2), blocked the rebound-contraction while selective desensitization of $P_{2Y}-purinoceptor$ with ${\alpha},{\beta}-MeATP$ did not affect it. ATP and 2-MeSATP induced smooth muscle contraction, which was effectively blocked by RB-2 and suramin, a nonselective $P_2-purinoceptor$ antagonist. Particularly, in the presence of RB-2, exogenous ATP and 2-MeSATP inhibited spontaneous phasic contractions, suggesting the existence of different populations of purinoceptors. Both the rebound-contraction and the agonist-induced contraction were not inhibited by indomethacin. The rank orders of agonists' potency were 2-MeSATP > ATP ${ge}$ UTP for contraction and ${\alpha},{\beta}-MeATP\;{\ge}\;{\beta},{\gamma}-MeATP$ for inhibition of the phasic contraction, that accord with the commonly accepted rank order of the classical $P_{2Y}-purinoceptor$ subtypes. Electrical activities of smooth muscles were only slightly influenced by ATP and 2-MeSATP, whereas ${\alpha},{\beta}-MeATP$ attenuated slow waves with membrane hyperpolarization. From the above results, it is suggested that ATP acts as an excitatory neurotransmitter, which mediates the rebound-contraction via $P_{2Y}-purinoceptor$ in guinea-pig gastric antrum.

• Korean Journal of Pharmacognosy
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• v.20 no.3
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• pp.188-195
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• 1989

Hyangsayangwee-Tang, a combined preparation of crude drugs, which has been used for stomach and intestinal disorder, was examined for anti-spasmodic, anti-ulcerative and anti-emetive effects. Spontaneous motility of isolated ileum was strongly suppressed and inhibitory effects against contraction of isolated ileum induced by acetylcholine and barium chloride were shown in mice. And, contraction of isolated guinea-pig ileum by histamine was inhibited. In rats fundus preparations, Hyangsayangwee-Tang elicited strong relaxation and had antagonist effects against the spasm induced by acetylcholine and barium chloride. A significant inhibitory effect on the intestinal propulsion of barium sulfate in mice was shown. In pylorus-ligated rats, Hyangsangwee-Tang inhibited gastric secretion and showed a strong anti-peptic activity. Protective effects against gastric ulceration induced by pyloric ligation, water-immersion stress, histamine and aspirin were significantly recognized in mice and rats. Hyangsayangwee-Tang decreased cupric sulfate-induced vomitting in frogs.

• The Korean Journal of Physiology
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• v.27 no.2
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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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• 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.

• The Korean Journal of Physiology
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• v.28 no.1
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• pp.51-59
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• 1994

This study was carried out to elucidate the excitatory mechanisms of Substance P in the antral circular muscle, using isometric contraction recording, conventional microelectrode method and whole-cell patch clamp technique. Substance P produced tonic and phasic contractions in a dose-dependent manner and depolarized membrane potential with increased amplitude of slow waves in muscle strips. Voltage-dependent $Ca^{2+}$ currents were increased by the application of Substance P from a holding potential of -60mV to 50mV in 10mV steps and this effect was blocked by the addition of an antagonist. Also Substance P increased transient and spontaneous oscillatory $K^+$ outward currents. The enhanced outward currents were abolished by apamin in dispersed single cells. These results suggest that the depolarization of membrane potential by Substance P activates voltage-dependent $Ca^{2+}$ channels, which represents an excitatory response in the antral circular muscle and led to an increase in $Ca^{2+}\;activated\;K^+\;currents$.

• Biomolecules & Therapeutics
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• v.6 no.2
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• pp.159-164
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• 1998

General pharmacological properties of recombinant human parathyroid hormone (hPTH) were examined. The administration of hPTH (7, 35 and 175 lU/kg sc) in mice had no effects in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazol solution. hPTH (9 and 44 lU/kg, sc) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration, and it did not influence the responses produced by injection of acetylcholine or epinephrine. It showed no direct effect at 4.4$\times$10$_{-2}$IU/ml in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also showed no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence intestinal propulsion at the doses of 7,35 and 175 lU/kg sc in mice. This drug exhibited no effect on urinary excretion at the doses of 7 and 35 lU/kg sc in rats. However, at a dose of 175 lU/kg sc, it showed a decreased urination along with decreased excretion of potassium, sodium and chloride ion. These results indicate that hPTH does not exert any of serious pharmacological effects except the inhibition of urination at a highest dose used.

• Biomolecules & Therapeutics
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• v.4 no.2
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• pp.154-161
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• 1996

General pharmacological properties of LB-00014, an erythropoietin which was produced by recombinant DNA technique in Biotech Research Institute, LG Chemical Ltd. were examined. The administration of LB-00014 (60, 600, 6000 IU/kg, iv) in mice had no effect in general behavior and central nervous system, and no influences on normal body temperature, writhing syndromes induced by 0.7% acetic acid solution and chemoshock produced by strychnine and pentetrazole solution. LB-00014 (60, 600, 6000 IU/kg, iv) given to anesthetized rabbits showed no effect on blood pressure of carotid artery and respiration rates, and it did not influence the responses produced by injection of acetylcholine or epinephme. The administration of LB-00014 (601, 600, 6000 IU/kg, iv) in rats had no effect on the plasma prothrombin time, activated partial thromboplastin time and hemolytic action. The platelet aggregation induced by collagen in human plasma was not influenced by LB-00014 (10, 100, 1000 lU/kg, iv). It showed no direct effect at 100 and 1000IU/m1 in isolated stomach fundus and uterus of rats and ileum of guinea-pig, and it also had no inhibition of contraction produced by acetylcholine, oxytocin, serotonin and histamine in the above-mentioned preparations. It did not influence gastric secretion, pH and acid output at 6000 IU/kg, iv in rats, but showed a significant increase in intestinal propulsion of mice at 6000 IU/kg, iv. Its administration (60, 600, 6000 lU/kg, iv) caused no effect on urine and electrolyte excretion in rats. These results indicate that LB-00014 does not exsert any of serious pharmacological effects.