• Title/Summary/Keyword: High $K^{+}$-induced contraction

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Vasodilating Mechanism of Dibutyryl-cAMP and Forskolin in Rabbit Aorta (Dibutyryl-cyclic AMP와 Forskolin의 혈관평활근 이완작용)

  • Ahn, Hee-Yul;Lim, Jung-Kyoo
    • The Korean Journal of Pharmacology
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    • v.26 no.2
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    • pp.127-133
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    • 1990
  • Dibutyryl-cyclic AMP (db-cAMP) and forskolin were used to investigate vasodilating mechanism of cAMP in rabbit aorta. Db-cAMP and forskolin inhibited the development of contractile tension induced by norepinephrine (NE) concentration-dependently. However, high $K{^+}-induced$ contractile tension was inhibited less effectively by db-cAMP and forskolin. Db-cAMP and forskolin inhibited $^{45}Ca^{2+}$ uptake increased by NE. Forskolin seemed to inhibit $^{45}Ca^{2+}$ uptake increased by high $K{^+}$, but this inhibition was not significant statistically. Db-cAMP inhibited $Ca^{2+}-transient$ contraction by NE in $Ca^{2+}-free$ solution. In conclusion, it seems that cAMP blocks $Ca^{2+}$ influx through receptor operated $Ca^{2+}$ channels (ROCs), but that the effect of cAMP on $Ca^{2+}$ influx through voltage gated $Ca^{2+}$ channels (VGCs) is not clear in this experiment. Furthermore, cAMP is likely to inhibit calcium release from the intracellular stores.

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Numerical investigation into flow noise source of a convergent-divergent nozzle in high pressure pipe system using wavenumber-frequency analysis (파수-주파수 분석을 통한 고압 배관 내 수축 확장 노즐의 유동 소음원에 대한 수치적 연구)

  • Ku, Garam;Lee, Songjune;Kim, Kuksu;Cheong, Cheolung
    • The Journal of the Acoustical Society of Korea
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    • v.36 no.5
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    • pp.314-320
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    • 2017
  • A pressure relief valve is generally used to prevent piping systems from being broken due to high pressure gas flows. However, the sudden pressure drop caused by the pressure relief valve produces high acoustic energy which propagates in the form of compressible acoustic waves in the pipe and sometimes causes severe vibration of the pipe structure, thereby resulting in its failure. In this study, internal aerodynamic noise due to valve flow is estimated for a simple contraction-expansion pipe by combining the LES (Large-Eddy Simulation) technique with the wavenumber-frequency analysis, which allows the decomposition of fluctuating pressure into incompressible hydrodynamic pressure and compressible acoustic pressure. In order to increase the convergence, the steady Reynolds-Averaged Navier-Stokes equations are numerically solved. And then, for the unsteady flow analysis with high accuracy, the unsteady LES is performed with the steady result as the initial value. The wavenumber-frequency analysis is finally performed using the unsteady flow simulation results. The wavenumber-frequency analysis is shown to separate the compressible pressure fluctuation in the flow field from the incompressible one. This result can provide the accurate information for the source causing so-called acoustic-induced-vibration of a piping system.

Ardipusilloside-I stimulates gastrointestinal motility and phosphorylation of smooth muscle myosin by myosin light chain kinase

  • Xu, Zhili;Liang, Hanye;Zhang, Mingbo;Tao, Xiaojun;Dou, Deqiang;Hu, Liping;Kang, Tingguo
    • The Korean Journal of Physiology and Pharmacology
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    • v.21 no.6
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    • pp.609-616
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    • 2017
  • Ardipusilloside-I is a natural triterpenoid saponin, which was isolated from Ardisia pusilla A. DC. The aim of the study was to evaluate the stimulation of ardipusilloside-I on gastrointestinal motility in vitro and in vivo. The experiment of smooth muscle contraction directly monitored the contractions of the isolated jejunal segment (IJS) in different contractile states, and the effects of ardipusilloside-I on myosin were measured in the presence of $Ca^{2+}$-calmodulin using the activities of 20 kDa myosin light chain ($MLC_{20}$) phosphorylation and myosin $Mg^{2+}$-ATPase. The effects of ardipusilloside-I on gastro emptying and intestinal transit in constipation-predominant rats were observed, and the MLCK expression in jejuna of constipated rats was determined by western blot. The results showed that, ardipusilloside-I increased the contractility of IJS in a dose-dependent manner and reversed the low contractile state (LCS) of IJS induced by low $Ca^{2+}$, adrenaline, and atropine respectively. There were synergistic effects on contractivity of IJS between ardipusilloside-I and ACh, high $Ca^{2+}$, and histamine, respectively. Ardipusilloside-I could stimulate the phosphorylation of $MLC_{20}$ and $Mg^{2+}$-ATPase activities of $Ca^{2+}$- dependent phosphorylated myosin. Ardipusilloside-I also stimulated the gastric emptying and intestinal transit in normal and constipated rats in vivo, respectively, and increased the MLCK expression in the jejuna of constipation-predominant rats. Briefly, the findings demonstrated that ardipusilloside-I could effectively excite gastrointestinal motility in vitro and in vivo.

Acute Toxicity and General Pharmacological Action of QGC EXT

  • Lee, Jong-Mi;Im, Wi-Joon;Nam, Yoon-Jin;Oh, Kyung-Hoon;Lim, Jae-Chun;Whang, Wan-Kyunn;Sohn, Uy-Dong
    • The Korean Journal of Physiology and Pharmacology
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    • v.16 no.1
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    • pp.49-57
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    • 2012
  • It has been shown that QGC isolated and purified from Rumecis folium found protective effects of gastritis and esophagitis which EXT is an ethanol extract of it. We examined acute toxicity and the general pharmacological action of QGC EXT to search for any side effects of it in rats, mice, guinea pigs, and cats. In a single dose toxicity study, QGC EXT didn't show toxicological effects in rats and mice, and the $LD_{50}$ was over 5 g/kg in both animals, and there were also no changes in weight, feed and water intake during these toxicological experimental periods. We examined the general pharmacological action on central controlled behavior responses, and peripheral organs including blood pressure, heart rate, respiration and gastrointestinal system, We found that there were no significant changes in body temperature, locomotors activity, stereotyped behaviors, sleeping time, and convulsion. In other studies, writhing reaction, normal body temperature, there did not appear to be any changes. The large intestine movement and electrical field stimulation-induced contraction was not changes by its EXT. In addition, the influences on blood pressure, heart rates, and respiration by QGC EXT were not found. These results indicate that QGC EXT may be very safe as a new drug, since its $LD_{50}$ was very high over 5 g/kg and any side effects were not found.

Arterial Pressor Response Elicited by Activation of Muscle Afferent Fibers in the Cat (고양이에서 근육감각신경 활성화로 유발된 승압반사)

  • Kim, Jun;Seo, Sang-A;Sung, Ho-Kyung
    • The Korean Journal of Physiology
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    • v.22 no.2
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    • pp.231-243
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    • 1988
  • This study was performed to investigate the mechanism of changes in arterial blood pressure, as a typical example of somatosympathetic reflex, induced by activation of muscular afferent nerves. Cats were anesthetized with ${\alpha}-chloraloae$ (60 mg/kg, i.p.). Afferent fibers in muscle nerve were activated by various method muscle contraction, electrical stimulation of muscle nerves, intraarterial injection of some algesic substances and noxious mechanical stimulation etc-and the evoked changes in arterial blood pressure were monitored. The effects of intravenous or direct spinal administration of morphine on the changes in arterial blood pressure induced by activation of the muscle afferent fibers were observed and also the effects of spinal lesions made in the $L1{\sim}L3$ spinal cord on them were studied to identify the ascending spinal pathways of the somatosympathetic reflexes. Followings are the results obtained. 1) The stimulation of medial gastrocnemius nerve under non-paralyzed condition with C-strength, low frequency (lower than 20 Hz) stimuli elicited a depressor response and a pressor response was elicited with C-strength, high frequency stimuli, of which the maximal response was observed at 100 Hz stimulation. 2) When the animal was paralyzed, depressor response to stimulation of the medial gastrocnemius nerve was observed with C-strength, $0.5{\sim}5Hz$ stimuli although the amplitude of the depressor response was decreased. The maximal pressor response was observed during stimulation with C-strength, $20{\sim}100Hz$ stimuli. 3) Intraarterial injection of some algesic substances induced marked pressor responses while noxious mechanical stimulation of the medial gastrocnemius muscle was not enough to elicit any significant changes (larger than 10 mmHg) in arterial blood pressure. 4) Systemically administered morphine (2 mg/kg) lowered the arterial blood pressure immediately and persistently and it was reversed by administration of naloxone. Direct spinally administered morphine did not elicit any changes. 5) The pressor response elicited by the activation of muscle afferent nerves was strengthened by systemic morphine administration while the depressor response tended to decrease. 6) Morphine administered on the spinal cord directly, decreased pressor response but did not change depressor response. From the above results it is concluded that there are separate groups of afferent nerves in the medial gastrocnemius nerve, which elicit pressor and depressor responses and the spinal ascending pathways of them are also separated from each other.

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The Altered Signaling on EFS-Induced Colon Contractility in Diabetic Rats

  • Thein, Wynn;Po, Wah Wah;Kim, Dong Min;Sohn, Uy Dong
    • Biomolecules & Therapeutics
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    • v.28 no.4
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    • pp.328-336
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    • 2020
  • Diabetes mellitus affects the colonic motility developing gastrointestinal symptoms, such as constipation. The aim of the study was to examine the role of intracellular signaling pathways contributing to colonic dysmotility in diabetes mellitus. To generate diabetes mellitus, the rats were injected by a single high dose of streptozotocin (65 mg/kg) intraperitoneally. The proximal colons from both normal and diabetic rats were contracted by applying an electrical field stimulation with pulse voltage of 40 V in amplitude and pulse duration of 1 ms at frequencies of 1, 2, 4, and 6 Hz. The muscle strips from both normal rats and rats with diabetes mellitus were pretreated with different antagonists and inhibitors. Rats with diabetes mellitus had lower motility than the control group. There were significant differences in the percentage of inhibition of contraction between normal rats and rats with diabetes mellitus after the incubation of tetrodotoxin (neuronal blocker), atropine (muscarinic receptor antagonist), prazosin (α1 adrenergic receptor antagonist), DPCPX (adenosine A1 receptor antagonist), verapamil (L-type Ca2+ channel blocker), U73122 (PLC inhibitor), ML-9 (MLCK inhibitor), udenafil (PDE5 inhibitor), and methylene blue (guanylate cyclase inhibitor). The protein expression of p-MLC and PDE5 were decreased in the diabetic group compared to the normal group. These results showed that the reduced colonic contractility resulted from the impaired neuronal conduction and decreased muscarinic receptor sensitivity, which resulted in decreased phosphorylation of MLC via MLCK, and cGMP activity through PDE5.

A Study on the Shrinkage of Silk Fabric by $Ca(NO_3){_2}$ Solution

  • Choi, Se-Min;Shin, Yu-Ju;Kim, Jong-Jun;Jeon, Dong-Won
    • Journal of Fashion Business
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    • v.13 no.3
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    • pp.136-148
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    • 2009
  • The phenomenon of the shrinkage of silk fibers induced by inorganic salts including LiBr, $Ca(NO_3){_2}$, and $CaCl_2$, has been studied up to the present as one of the finishing methods of silk. It is expected that the shrinkage phenomenon may greatly contribute to the realization of the high sensibility of silk fibers. Especially the shrinkage enables the expression of three-dimensional appearance of silk fabrics along with the improvements in dimensional stability, resilience in stretching, and comfort. Numerous theoretical studies on the contraction phenomenon by $Ca(NO_3){_2}$ have been conducted so far. These studies have focused mostly on the silk fibers. It is difficult to find studies on silk fabrics. The negative aspects of the finishing are such as strength drop, yellowish discoloration, and fiber damage. These should also be considered as well as the positive aspects. In this study, the phenomenon of salt shrinkage is diversely reviewed by applying $Ca(NO_3){_2}$ solution for the silk fabrics as objects. The changes in the air permeability, thickness, and color were investigated with focus on the shrinkage of the silk fabrics according to the changes in treatment conditions. Some findings from this study are as follows: Within short period of time at the initiation of salt shrinkage, the salt shrinkage proceeds effectively. In the case of concentration of 47.4%, or 46.3% of $Ca(NO_3){_2}$ solution, appropriate treatment time seems to be 20seconds, or $2{\sim}8$minutes, respectively. Excessive shrinkage is obtained when lower liquor ratio is adopted. As a result, the condition is acting extremely disadvantageously against the thickness and yellow discoloration aspects.

Antihypertensive Effects of Enantiomers of Amlodipine Camsylate, a Novel Salt of Amlodipine

  • Oh, Kwang-Seok;Kim, Maeng-Sup;Lee, Byung-Ho
    • Biomolecules & Therapeutics
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    • v.15 no.1
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    • pp.40-45
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    • 2007
  • The vascular relaxant effects on isolated rat aorta of amlodipine camsylates (S-, R-enantiomer, and R/S-racemate), were evaluated and compared with that of S-amlodipine besylate. Furthermore, antihypertensive effects were measured in spontaneously hypertensive rat (SHR). The S-amlodipine camsylate concentration-dependently inhibited $Ca^{2+}$-induced contraction of rat aorta with a very slow onset of action (reached its maximum at 3.5h; $ED_{50}:\;1.50\;{\pm}\;0.24$ nM), having a potency 2-fold higher than those of R/S-amlodipine camsylate $(ED_{50}:\;3.36\;{\pm}\;0.91\;nM)$ and similar to those of S-amlodipine besylate $(ED_{50}:\;1.44\;{\pm}\;0.14\;nM)$, whereas the R-amlodipine camsylate has 590-fold lower vasorelaxant activity $(ED_{50}:\;886.4\;{\pm}\;49.7\;nM)$. In SHR, orally administered S-amlodipine camsylate produced a dose-dependent and long-lasting (>>10 h) antihypertensive effect $(ED_{20}:\;0.89\;mg/kg)$, with a potency 2-fold higher than those of R/S-amlodipine camsylate $(ED_{20}:\;1.82\;mg/kg)$ and similar to those of S-amlodipine besylate $(ED_{20}:\;0.71\;mg/kg)$. In contrast, the R-amlodipine camsylate has no effect even-though administrated high concentration 10 mg/kg. These results suggest that S-amlodipine camsylate has the potency and long-lasting antihypertensive activity as single enantiomer drug, and its antihypertensive effect is not significantly different to that of S-amlodipine besylate.

Effects of Lemakalim, a Potassium Channel Opener, on the Contractility and Electrical Activity of the Antral Circular Muscle in Guinea-Pig Stomach

  • Kim, Sung-Joon;Jun, Jae-Yeoul;Choi, Youn-Baik;Kim, Ki-Whan;Kim, Woo-Gyeum
    • 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.

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Regional Differences in Voltage-tension Relationship of Gastric Smooth Muscles in Guinea-pig (위 평활근의 부위별 전압-장력 관계에 관한 연구)

  • Kim, Ki-Whan;Lee, Sang-Jin;Suh, Suk-Hyo
    • The Korean Journal of Physiology
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    • v.23 no.2
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    • pp.263-275
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    • 1989
  • Mechanical contractions and electrical activities of the fundic longitudinal and antral circular muscle fibers were investigated in order to elucidate topical differences of gastric motility. K-induced contracture was produced by exposure of muscle strips to high K Tyrode solution. Membrane potential and mechanical contraction were simultaneously recorded by conventional glass microelectrode method and single sucrose-gap technique. All experiments were performed in tris-buffered Tyrode solution which was aerated with $100%\;O_2\;and\;kept\;35^{\circ}C$. The results obtained were as follows: 1) The resting membrane potential of circular muscle cells in the antral region was about 10 mV more negative than that in the fundic region. 2) The membrane potentials decreased almost linearly as the extracellular KCI concentration was increased both in antral circular muscle cells and in fundic longitudinal muscle cells. 3) The thresholdal K concentration of K-contracture was 15 mM (membrane potential, -48 mV) for the antral circular muscle strip and 20 mM for the fundic longitudinal muscle cells. 4) The ratio of membrane permeability coefficient for $Na^+\;and\;K^+,\;P_{Na}/P_K\;({\alpha})$ was 0.065 for antral circular muscle cells and was 0.108 for fundic longitudinal muscle cells. 5) K-contracture of antral and fundic smooth muscle strips showed the contracture composed of phasic and tonic components. The amplitude of the phasic component increased sigmoidally in a dose-dependent manner, whereas that of the tonic component was maximal at a concentration of 40 mM KCI and at the concentrations above or below 40 mM KCI the amplitude was reduced. 6) The inverse relationship between the amplitude of tonic component and extracellular KCI concentration in the range of 40 to 150 mM KCI was more prominent in the antral circular muscle strip than in the fundic longitudinal muscle strip, where the amplitude of the tonic component decreased less steeply and was maintained higher at the same high K concentrations. 7) The tonic component was totally dependent on the external $Ca^{2+}$ and completely abolished by verapamil, while tile phasic component was far less dependent on the external $Ca^{2+}$ and partially suppressed by verapamil. From the above results, the following conclusions could be made. 1) The phasic component of K-contracture is produced both by intracellular $Ca^{2+}$ mobilization and by $Ca^{2+}$-influx from outside, while the tonic component is generated and maintained by the $Ca^{2+}-influx$ through the potential-dependent $Ca^{2+}$ channel. 2) The mechanism of reducing the free $Ca^{2+}$ concentration in the myoplasm seems to be more developed in the antral circular muscle than in the fundic longitudinal muscle. 3) The lower resting membrane potential of the fundic longitudinal muscle cell reflects a relatively high $P_{Na}/P_K$ ratio of about 0.108.

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