• The Korean Journal of Physiology
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• v.4 no.2
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• pp.45-51
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• 1970

In an attempt to better understand the effect of whole body irradiation on the spontaneous motility and oxygen consumption rate of the isolated mouse duodenum, a whole body X-irradiation of 1,000r. was given to albino mouse, and 1) the total length of contraction of isolated duodenum was recorded on kymograph every five minutes for 60 minutes, 2) glucose and 5-hydroxytryptamine(5-HT) were added to the reaction medium of Kreb's-Ringer-bicarbonate buffer(KRB) and response of the isolated duodenum to the drugs was observed, and 3) the oxygen consumption rate $(QO_2)$ of the isolated duodenum as well as the effect of glucose and 5-HT on $QO_2$ were measured by Warburg's standard manometric method and the comparison was made with the control(i.e. normal) group. The results thus obtained are summarized as follows. 1. The spontaneous motility of the isolated duodenum in the irradiated groups showed a significantly elevated pattern for the first 15 minutes comparing with the control. The motility, however, decreased after 15 minutes and remained so in the irradiated groups to the level of the nonirradiated control, but 24 hours post-irradiation group showed a tendency of an increased motility while one hour post-irradiation group showed no difference comparing with the control. 2. Addition of glucose produced generally elevated motility of the isolated duodenum in both irradiated and non-irradiated groups comparing with the control throughout the experiment, but no difference was observed in contractile amplitude between the irradiated and non·irradiated groups. 3. When 5-HT was added to the irradiated group, the contractile amplitude of isolated duodenum was similar to that of the control, and 5-HT alone caused a slight increase of the motility comparing with the control. 4. The oxygen consumption rate $(QO_2)$ of the isolated duodenum was found to be ,slightly increased in one hour post·irradiated group, but similar in 24 hour post·irradiated group comparing with the control. Glucose produced a significant increase of $QO_2$ in all the groups, but 5-HT produced a tendency of decrease of $QO_2$ in all the groups.

• 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.

• Korean Journal of Pharmacognosy
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• v.21 no.2
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• pp.163-172
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• 1990

These studies were conducted to investigate the effects of Tongkwan-San water extract on analgesic, sedatative, anti-inflammatory, blood pressure and vasodilating actions, the relaxing action of isolated ileums and actions on the contact dermatitis induced by picryl chloride and on the leakage of the dye into the peritoneal cavity. The results of these studies were summarized as follows: The analgesic effect of Tongkwan-San was noted. The prolongation of anesthetic time of Tongkwan-San was recognized. Spontaneous motilities of isolated ileum of mice were strongly suppressed by Tongkwan-San. It inhibited the contractions of isolated ileum of mice induced by acetylcholine and barium chloride and the contraction of isolated ileum of guinea-pig induced by histamine. Inhibition of the contact dermatitis induced by picryl chloride was recognized. Anti-inflammatory effects in the paw edema induced by histamine and dextran were significantly shown. The leakage of dye into the peritoneal cavity in mice was significantly inhibited. Hypotensive and vasodilating action due to vascular smooth muscle relaxation were noted in rats and rabbits.

• 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.4
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• pp.406-411
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• 1998

The pre-mixed $_{13}C$-urea powder preparation in ${Helikit}_{TM}$ for test of Helicobacter pylori was evaluated for pharmacological properties. The oral doses of the preparation used in mice were 30-fold as compared to human doses. The results obtained in the present study demonstrate that spontaneous movement, hexobarbital-induced hypnosis, rotarod performance, body temperature, acetic acid-induced writhing syndrome, chemical and electroshock convulsion, pupil size and intestinal propulsion had not been affected at the oral doses of 230, 700 and 2100 mg/kg in mice. The blood pressure was slightly elevated as given intravenously in rats at a dose of 5 mg/kg of the preparation, but respiration was not influenced at the dose. In isolated guinea pig ileum and rat fundus preparation, the preparation at a concentration of $1{\times}10^{4}$ g/ml neither caused any direct effect nor inhibited the contraction produced by acetylcholine, histamine or 5-hydroxytryptamine. These results reported here provide evidence that pre-mixed $^{13}C$ 13/C-urea powder preparation is free of general pharmacological properties performed in oral administration.

• Biomolecules & Therapeutics
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• v.4 no.4
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• pp.385-390
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• 1996

General pharmacological properties of urinary trypsin inhibitor (UTI) following intravenous administration of 1,000,000 units/kg were examined in terms of effects on central nervous system, cardiovascular system, respiratory system, gastrointestinal system in mice, rats and rabbits. Administration of UTI (1,000,000 units/kg, iv) had no effect on central nervous system; no influences on pentobarbital sleeping time, spontaneous activity, normal body temperature, chemoshock produced by pentylenetetrazole solution, writhing syndromes induced by 0.6% acetic acid solution, and motor coordination of mice. The administration of UTI (1,000,000) units/kg, iv) in rats had no effect on systolic blood pressure and pulse rate. UTI (500,000 units/kg, iv) given to anesthetized rabbits showed no effect on respiratory rate. However, it showed significant elevation of respiratory rate at the concentration of 1,000,000 units/kg. Gastric secretion of rat and intestinal motility of mice were not influenced by the dose of 1,000,000 units/kg. In terms of autonomic nervous system, the material did not show direct effect and inhibitory or augmentative action of histamine- or acetylcholine-induced contraction at the concentration of 2,000 units/ml in the isolated ileum of guinea pig.

• The Journal of Internal Korean Medicine
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• v.15 no.2
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• pp.229-239
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• 1994

KUNLITANG(建理湯) have been widely used in the disease of digestive system, which was based on the oriental references. In order to investigate the clinical effect of it, the experimental works were carried out with mice and rats. The following results have been obtained : 1. The analgesic effect in mice was recognized in acetic acid method. 2. The inhibitory effect on transfortation activity in small intestine of mice was recognized. 3. In the experiment to see the effects of KUNLITANG on the gastric juice in rats, volumn, free HCL and total acidity were decreased, pepsin activity was inhibited. Whi1e pH was increased by the administration of KUNLITANG, respectably. 4. In the experiment to see the effects of KUNLITANG on the gastric ulcers in rats, anti-ulcerative effects were recognized in Shay rats and induced by histamine or aspirine. 5. Spontaneous contraction in the isolated ileum in rats was inhibited. According to the above experimental results, it can be concluded that KUNLITANG are very effective on many gastrointestinal diseases of biwihehanheung(脾胃虛寒型)

• Biomolecules & Therapeutics
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• v.14 no.4
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• pp.194-201
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• 2006

The general pharmacological properties of GCSB-5, a herbal formulation consisting of 6 Oriental herbs(Ledebouriellae Radix, Achyranthis Radix, Acanthopanacis Cortex, Cibotii Rhizoma, Glycine Semen and Eucommiae Cortex), were investigated in mice, rats, guinea pigs and rabbits. The administration of GCSB-5 had no effect on general behavior, and did not influence the central nervous system. Mean blood pressure, heat1 and respiratory rate and contractile response of the isolated guinea pig atrium were unaffected by the treatment of GCSB-5. Addition of GCSB-5 did not cause spontaneous relaxation and contraction of the isolated guinea pig ileum and rat uterus. And also, GCSB-5 had no effect on the gastrointestinal system and the blood system of the animals examined in this study. GCSB-5, at higher doses(1,000 and 3,000 mg/kg), increased the urinary excretion of electrolytes, however, the urine volume and pH in rats were unaffected. Taken together, these results indicate that GCSB-5 does not induce any adverse effects in experimental animals and is expected to have no significant general pharmacological activities.

• The Korean Journal of Physiology
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• v.22 no.2
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• pp.189-206
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• 1988

The effects of ouabain on the contractile and electrical activities were investigated in the isolated preparations of guinea-pig taenia coli, and compared with those of vanadate. Spontaneous contractions were recorded with force transducer, and electrical activites were measured by use of suction electrode, or single sucrose-gap technique. The contractions were induced by the electrical stimulation for 5 seconds every 1 minute with alternating current (60 Hz, 3.0 V/cm) through the platinum electrodes located in parallel with the long axis of the preparation. 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) Responses of spontaneous contractions to ouabain were concentration-dependent; $10^{-7}M$ ouabain caused a rise of basal tone. Above the concentration of $10^{-6}M$ ouabain, an initial increase followed by a decrease in tension was observed. 2) A continuous spike discharge was induced by the administration of $10^{-7}M$ ouabain. Above $10^{-6}M$ ouabain, a transient initial increase followed by a decrease in spike frequency and amplitude was produced, and finally membrane potential was sustained at a certain level without a spike discharge. 3) The characteristic response to $10^{-7}M$ ouabain was not blocked by the pretreatment with $10^{-7}M$ atropine. 4) The electrically induced contractions were completely suppressed at the concentration of $2{\times}10^{-7}M$ ouabain. These contractions were blocked more rapidly in paralled with the increase in ouabain concentration. 5) Effects of vanadate on the spontaneous activities were quite different from those of ouabain; $10^{-6}M$ vanadate increased the amplitude of contractions and $10^{-5}M$ vanadate increased slightly both amplitude and frequency of spontaneous contractions. $10^{-4}M$ vanadate showed irregular phasic contractions superimposed on the increased basal tone. 6) $10^{-5}M$ vanadate depolarized the membrane potential and shortened the interval between the bursts of spike discharge, whereas $10^{-4}M$ vanadate induced continuous spike discharge with membrane depolarization. 7) Vanadate caused a characteristic inhibitory response to the contractions induced by electrical stimulation; An initial rapid inhibition of tension development and then gradual recovery to a certain level. From the above results, the following conclusions could be made: 1) The rise of basal tone at $10^{-7}M$ ouabain is due to continuous spike discharge without a silent period. The continuous spike discharge is likely to be associated with a slight membrane depolarization caused by the blockage of Na pump. 2) The biphasic response induced by above $10^{-6}M$ ouabain seems to occur by the different mechanisms. The initial increase in tension is associated with depolarization along with an increase in spike frquency, whereas the subsequent relaxation occurs through a non-electrical mechanism. 3) The characteristic response to $10^{-7}M$ ouabain is resulted not from the action on intrinsic nerve terminal, but from its direct action on the membrane of smooth muscle cells. 4) The phasic contractions superimposed on the increased basal tone at the concentration of $10^{-4}M$ vanadate is resulted from the continuous spike discharge with membrane depolarization, of which mechanism remains unknown. 5) The inhibitory action of ouabain on the electrically induced contractions suggests that the increasein intracellular Na in some way inhibits the electrically induced $Ca^{2+}$ influx. The mechanism of vanadate action on the induced contractions remains unknown.

• The Korean Journal of Physiology
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• v.22 no.1
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• pp.13-29
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• 1988

In order to elucidate the regulatory mechanism of intracellular calcium ion concentrations, contractions or contractures induced by $Na^{+}-removal$, calcium-application or ouabain-treatment as an index of $Na^+/Ca^{2+}$ exchange activity were studied in atrial muscle or vascular smooth muscle (aorta and renal artery) of the rabbit. The magnitude of low sodium contractures in atrial trabeculae increased with sigmoid shape when external sodium concentrations were reduced to sodium-free condition, whereas that of calcium contracture intensified in a parabolic pattern when external calcium concentrations were elevated to 8 mM. $Na^{+}-removal$ contractures were induced in a duration-dependent manner to $K^{+}-free$ exposure and same findings were observed with ouabain treatment. $Na^{+}-free$ contractures were not affected by verapamil treatment, but stimulated by $100{\mu}M\;Mn^{2+}$ and inhibited by high concentrations of $Mn^{2+}\;(2{\sim}8mM)$ in a dose-dependent manner. Ryanodine which is known to suppress the release of calcium from internal store abolished spontaneous twitch contractions induced by $K^{+}-free$ solution, but had no effect on the development $Na^{+}-free$ contractures. Na-free contractures were not always induced in vascular smooth muscle preparations. Contractures by $O\;mM\;Na^+$ were usually seen in aorta, but not often in renal artery.$50\;mM\;K^+$, noradrenaline (NA) and angiotensin II (AII) always evoked very large contraction in all preparations of vascular smooth muscle. Contractures developed by $O\;mM\;Na^+$ were not sensitive to verapamil treatment as in atrial trabeculae, but were abolished by $100{\mu}M\;Mn^{2+}$. In contrast to $Na^{+}-free$ contractures, $Mn^{2+}(100{\mu}M)$ had no effect on the contractures induced by NA or 50 mM$K^+$. Caffeine in the concentration of 10 mM evoked transient contracture in the distal renal artery. The rate of spontaneous relaxation in caffeine contracture was dependent upon the concentrations of external sodium, and had double component of relaxation when the rate of relaxation was plotted in the semilogarithmic scale of relative tension versus time. Especially late components of relaxation had more direct relation to $Na^+$ concentrations. It could be concluded that $Na^+/Ca^{2+}$ exchange mechanism in the heart has a large capacity, inhibited by $Mn^{2+}$ but not by verapamil and ryanodine, while $Na^+/Ca^{2+}$ exchange system in vascular smooth muscle has a very low capacity especially in small artery, inhibited by low concentration of $Mn^{2+}\;(100{\mu}M)$ but not affected by verapamil and ryanodine.