• The Korean Journal of Physiology
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• v.24 no.1
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• pp.91-102
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• 1990

The effects of extracellular $Ca^{2+}$ and various $Ca^{2+}$ antagonists on endothelium-dependent relaxation to acetylcholine were studied in the isolated rabbit thoracic aorta in order to elucidate the control mechanism of endothelium derived relaxing factor (EDRF) release. Endothelium was removed from aortic strips by gentle rubbing with cotton ball. The effect of hemoglobin on basal tension was also observed with hemolysate. The results obtained were as follows: 1) Endothelium-dependent relaxation (EDR) to acetylcholine (ACh) showed biphasic pattern; the initial rapid relaxation phase and the late slow relaxation phase. 2) With the depletion of the extracellular $Ca^{2+}$, EDR was gradually suppressed, especially the late slow relaxation. 3) Verapamil, nifedipine, $Mn^{2+}$ and $Cd^{2+}$ had not any effect on EDR, while $La^{3+}$ and $Co^{2+}$ suppressed EDR completely. 4) The resting tension of the strips with rubbed endothelium was not altered by the addition of hemoglobin. That of the strips with intact endothelium, however, was enhanced and EDR to ACh was completely blocked From these results, we suggest that extracellular $Ca^{2+}$ is necessary for ACh-induced slow relaxation while $Ca^{2+}$ antagonists have not any effect on EDR.

• YAKHAK HOEJI
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• v.41 no.3
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• pp.335-344
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• 1997

The absorption, distribution and excretion of $^{14}C$ labeled YH1885 {5,6-Dimethyl-2(4-fluorophenylamino)-4-(1-methyl-1,2,3,4-tetrahydroisoquinolin-2-yl)pyrimidine hydroc hloride), a new proton pumpinhibitor, were investigated in rats after a single administration of $^{14}C$-YH1885. 1. After intravenous administration of 5mg/kg, the blood level of radioactivity declined in a biphasic fashion with the mean terminal elimination half-life of 12.4hr. 2. After oral administration of 20mg/kg, the maximum blood level of radioactirity was reached at 4.0hr in female rats. The blood level of radioactivity-time profiles in male and female rats were similar, and the absorptionof $^{14}C$-YH1885 was not affected by food. 3. Appproximately 89% and 1% of radioactivity of the total dose were excreted in feces and urine, respectively. 4. Biliary excretion of radioactivity was 47.9% of the dose. Enterohepatic circulation of radioactivity was 49.6%. 5. Radioactivity was excreted maily into feces via bile. 6. The concentration of radioactivity in most tissues reached the peak level at 4.0hr after dosing, and then declined. Autoradiograms of male rats showed that the radioactivity levlels in the fat, harder's gland, liver and G-Itract were higher than those in the other tissues and the elimination of radioactivity from fat and liver was slow. 7. Autoradiograms of a pregnant rat showed that radioactivity was transferred to mammary gland, placenta and fetus. The radioactivity level in the mammary gland was higher than that in the blood.

• Journal of the korean academy of Pediatric Dentistry
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• v.25 no.4
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• pp.788-796
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• 1998

The purpose of this study was to investigate the effect of various electroacupuncture duration induced by acupuncture point-Zusanli ($S_{36}$) electrical stimulation on inhibition of amplitude of digastric electromyogram (dEMG) evoked by noxious electrical stimuli around the mental foramen. intraperitoneal sodium pentobarbital in an initial dose of 50mg/kg and maintenance doses of 4.5mg/kg/h were given through a cannula in the femoral vein using a constant infusion pump. A pair of stimulating electrodes were inserted for noxious stimuli around the mental foramen. An irritant electronic stimuli pulse (0.2 Hz, 0.1 ms duration) was produced with an intensity of about $1.5{\times}2$ times threshold for evoking the dEMG. The anterior belly of the digastric muscle was exposed and a pair of 0.1mm wire electrodes were inserted for dEMG recording. Acupuncture point stimulation on Zusanli (2 Hz, 250 ${\mu}s$, biphasic pulse, 2 V) was delivered by Dental Electronic Anesthesia (3M, U.S.A). For periods of electronic stimulation of 10, 20, and 30min, the amplitudes of dEMG were measured on the oscilloscope and on the monitor connected to the amplifier. The following results were obtained: The dEMG was decreased to 73.4% of that in the control set after 10 min electroacupunture stimulation (Group I); The dEMG was decreased to 77.1% (10min), 54.0.% (20min) of that in the control set after 20minutes of electroacupunture stimulation (Group II). The dEMG was decreased to 73.3% (10min), 61.9% (20min), 76.2% (30min) of that in the control set after 30 min of electroacupunture stimulation (Group III). From these results, it may be that in the electroacupuncture stimulation on the Zusnali resulted in a reduction of amplitude of dEMG and that the most effective electroacupuncture stimulation period was 20min.

• Biomolecules & Therapeutics
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• v.25 no.4
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• pp.452-459
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• 2017

In this study, the effect of particle size of genistein-loaded solid lipid particulate systems on drug dissolution behavior and oral bioavailability was investigated. Genistein-loaded solid lipid microparticles and nanoparticles were prepared with glyceryl palmitostearate. Except for the particle size, other properties of genistein-loaded solid lipid microparticles and nanoparticles such as particle composition and drug loading efficiency and amount were similarly controlled to mainly evaluate the effect of different particle sizes of the solid lipid particulate systems on drug dissolution behavior and oral bioavailability. The results showed that genistein-loaded solid lipid microparticles and nanoparticles exhibited a considerably increased drug dissolution rate compared to that of genistein bulk powder and suspension. The microparticles gradually released genistein as a function of time while the nanoparticles exhibited a biphasic drug release pattern, showing an initial burst drug release, followed by a sustained release. The oral bioavailability of genistein loaded in solid lipid microparticles and nanoparticles in rats was also significantly enhanced compared to that in bulk powders and the suspension. However, the bioavailability from the microparticles increased more than that from the nanoparticles mainly because the rapid drug dissolution rate and rapid absorption of genistein because of the large surface area of the genistein-solid lipid nanoparticles cleared the drug to a greater extent than the genistein-solid lipid microparticles did. Therefore, the findings of this study suggest that controlling the particle size of solid-lipid particulate systems at a micro-scale would be a promising strategy to increase the oral bioavailability of genistein.

• Biomedical Science Letters
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• v.6 no.4
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• pp.229-235
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• 2000

In situ brain-pancreas perfusion was performed on male adult Sprague-Dawley rats, of which the central nervous systems (CNS) were intact during the perfusion procedure. The modified Krebs-Ringer buffer with 100 mg/dL of glucose and 20 mM of arginine was perfused for 30 min. In the experimental groups, a cephalic glucopenia was induced at 0 min (GLP1 group) or at 16 min (GLP2 group). The glucopenia was not induced in the control (CONT group). Insulin and glucagon concentrations in the effluent samples from the pancreas were measured using a RIA method. In all three groups, the first and second phases in the dynamics of the insulin and glucagon secretion were observed, which was a typical biphasic secretory pattern. The amount of insulin secretion tended to decrease in the GLP1 and GLP2 groups, but there was no statistically significant difference among the groups. However, the amount of glucagon secretion during 0~15 min of the perfusion period in the GLP1 group was greater as compared to the CONT group (p<0.05). The amount of glucagon secretion during 16~30 min of the perfusion period in the GLP2 group tended to be greater as compared to the CONT group, however there was no statistical significance. These data indicate that the cephalic glucopenia stimulates the direct secretion of glucagon from the pancreas during the early period of perfusion in the CNS-intact pancreatic perfused rats.

• The Korean Journal of Physiology
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• v.18 no.2
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• pp.139-150
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• 1984

Vanadate is a potent inhibitor of Na-K-ATPase. Ouabain, the another specific inhibitor of Na-K-ATPase, induces the contraction in cardiac muscle and smooth muscle. But, some investigators observed the discrepancies between vanadate and ouabain-induced contraction in cardiac muscle. The difference of vanadate and ouabain-induced contraction was investigated in the cat ileal smooth muscle. The following results were obtained. 1) Ouabain-induced contraction was biphasic, but vanadate-induced contraction had one peak. 2) Atropine inhibited ouabain·induced contraction, but did not inhibit vanadate-induced contraction. 3) Changes in external $Ca^{++}$concentration or $Ca^{++}$ antagonists had a greater influence on the contraction induced hy vanadate than by ouabain. 4) Removal of $Na^+$ from incubation medium and high $K^+$ abolished ouabain-induced contraction, but had no effect on vanadate-induced contraction. 5) Vanadate-induced contraction was potentiated in the presence of ouabain. 6) After 3 hrs incubation with vanadate, there was no change in intracellular $Na^+$ concentrations in contrast with ouabain. These results suggest that vanadate contracts ileal smooth muscle through the mechanism different from ouabain, and this is independent of the inhibition of Na-K-ATPase activity.

• The Korean Journal of Physiology and Pharmacology
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• v.1 no.4
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• pp.425-434
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• 1997

Many reports represent that angiotensin II (ANG II) caused a dose dependent biphasic effects on fluid transport in the proximal tubule. However, respective roles of different signaling pathways in mediating these effects remain unsettled. The aim of the present study was to examine signaling pathways at high doses of ANG II on the $Na^+$ uptake of primary cultured rabbit renal proximal tubule cells(PTCs) in hormonally defined serum-free medium. High concentrations of ANG II $(>10^{-9}\;M)$ inhibited $Na^+$ uptake and increased $[Ca^{2+}]_i\;level$ in the PTCs. However, low concentrations of $(<10^{-11}\;ANG\;II)$ stimulated $Na^+$ uptake and did not affect $[Ca^{2+}]_i\;level$. 8-(N, N-diethylamino)-octyl-3,3,5- trimethoxybenzoate (TMB-8), ethylene glycol-bis$({/beta}-amino\;ethyl ether)-N,N,N'$, N'-tetra acetic acid (EGTA), and nifedifine partially blocked the inhibitory effects of ANG II on $Na^+$ uptake. When ANG II and bradykinin (BK) were treated together, $Na^+$ uptake was further reduced $(88.47{\pm}1.98%\;of\;that\;of\;ANG\;II,\;81.85{\pm}1.84%\;of\;that\;of\;BK)$. In addition, W-7 and KN-62 blocked the ANG II-induced inhibition of $Na^+$ uptake. Arachidonic acid reduced $Na^+$ uptake in a dose-dependent manner. When ANG II and arachidonic acid were treated together, inhibitory effects on $Na^+$ uptake significantly exhibited greater reduction than that of each group, respectively. When PTCs were treated by mepacrine $(10^{-6}\;M)$ and AACOCF3 $(10^{-5}\;M)$ for 1 hr before the addition of $(<10^{-9}\;ANG\;II)$, the inhibitory effect of ANG II was reversed. In addition, econazole $(>10^{-6}\;M)$ blocked ANG II-induced inhibition of $Na^+$ uptake. In conclusion, the $[Ca^{2+}]_i$ (calcium-calmodulin-dependent kinase) and phospholipase $A_2\;(PLA_2)$ metabolites are involved in the inhibitory effects of ANG II on $Na^+$ uptake in the PTCs.

• Applied Biological Chemistry
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• v.24 no.3
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• pp.186-193
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• 1981

Three fractions of carboxymethyl-cellulase (F-I, F-II, and F-III) and ${\beta}-glucosidase$ form Aspergillus niger were partially purified by ammonium sulfate fractionation. Sephadex G-150 and DEAE-Sephadex column chromatography. The optimum conditions such as pH and temperature and thermal inactivation properties of the enzymes were investigated. Arrhenius plots of F-II and F-III appeared as straight lines, whereas that of F-I was biphasic. The Z-values of F-II and F-III were $8^{\circ}C$ and $10^{\circ}C$ respectively, while that of F-I was $4^{\circ}C$ over $60{\sim}70^{\circ}C$ and $383^{\circ}C$ over $70{\sim}98^{\circ}C$. Three fractions and the crude extract of carboxymethyl-cellulase exhibited a similar optimum pH 4.3 and temperature of $60^{\circ}C$, while Z-value of crude extract $(21.5^{\circ}C)$ was much higher than that of the purified enzyme. Maximum activity of both purified and crude extract of ${\beta}-glucosidase$ was shown at pH 4.7 and $60^{\circ}C$, and z-value of the enzyme was $7^{\circ}C$.

• Journal of Chest Surgery
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• v.29 no.5
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• pp.487-494
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• 1996

The neurogenic responses of tracheal smooth muscles to electrical field stimulation (EFS) is biphasic, consisting firstly of cholinergic contraction followed by a slow and sustained relaxation. It is well known that a sustained relaxation involves the inhibitory non-adrenergic non-cholinergic systems. This study was done to Investigate the relaxing agents and their action mechanisms by use of an organ bath with plati- ilum . The tracheal smooth muscle relaxation due to EFS was suppressed by L-NAME, the WO (Nitric Oxide) synthase inhibitor, and these effects were reversed by L-arginine, the precursor of NO. Also, L-WAME (HG-nitro-L-arginine methyl ester) increased the basal tension. Nitroprusside, the NO-donor, suppressed the tracheal basal tension greatly. Methylene blue, the inhibitor of guanylate cyclase, decreased EFS-induced relaxations and increa ed basal tension. Forskolin and isoprenaline, which are activators of adenylate cyclase, suppressed tracheal basal tension in the same way as nitroprusside. TEA (tetraethylammonium), the non-specific K'channel blocker, and apamin, the Ca"-activated K'channel blocker, increased tracheal basal tension and EFS-induced relaxations. Our results indicate that Pr3 Is released upon stimulation of the NANC (Won Adrenergic Won Cholinergic) nerves in guinea-pig tracheal smooth muscle and that the release of NO related with the K+ channel, as well as the release of other inhibitory agents< e. g.)VIP (Vasoactive Intestinal Polypeptide), PHI (Peptide Histidine Isoleusine) > mediated via CAMP (cyclic Adenosine Monophosphate) may be Involved In sustained relaxation.

• The Korean Journal of Pharmacology
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• v.32 no.2
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• pp.189-199
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• 1996

Myocardial ${\alpha}_1-adrenoceptors$ have been shown to mediate a biphaslc inotropic response that was characterized by a transient decline followed by a sustained increasing phase in guinea pig ventricular muscle. Recently one group reported that an ${\alpha}_1-adrenoceptors-induced$ intracellular $Na^+$ decrease is linked to fast $Na^+$ channel inhibition and another group reported that it is linked to $Na^+$-$K^+$ pump activation by ${\alpha}_{1b}-adrenoceptors$. But until now, its mechanism is not clear. Therefore, to see whether the $Na^+$channel or $Na^+-K^+$ pump is related to a decrease in intracellular $Na^+$ activity and/or the negative inotropic response, and which ${\alpha}_1-adrenoceptor$ subtype was involved in the decrease in intracellular $Na^+$activity by phenylephrine, we used conventional and sodium selective microelectrodes, and tension transducer to determine the effects of ${\alpha}_1-adrenergic$ stimulation on membrane potential, intracellular $Na^+$ activity, and twitch force in guinea pig ventricular muscles. $10^{-5}$ M Phenylephrine produced a slight hyperpolarization of the diastolic membrane potential, a decrease or increase in $a_N^i_a$, and a biphasic inotropic response. The negative inotropic response accompanied by a decrease in intracellular $Na^+$activity, whereas in muscles showing a remarkable positive inotropic response without initial negative inotropic effect was accompanied by an increase in intracellular $Na^+$ activity. The decrease in intracellular $Na^+$ activity was apparently inhibited by WB4101, an antagonist of the ${\alpha}_{1a}-adrenoceptors$. The decrease in intracellular $Na^+$ activity caused by phenylephrine was not abolished or reduced by a block of the fast $Na^+$ channels. $V_{max}$ also was not affected by phenylephrine. Phenylephrine produced an increase in intracellular $Na^+$ activity in the presence of a high concentration of extracellular $Ca^{2+}$ (in quiescent muscle) or phorbol dibutyrate, a protein kinase C activator(in beating muscle). These suggest that the ${\alpha}_{1a}-adrenoceptors-mediated$ decrease in intracellular $Na^+$ activity may be related to the protein kinase C.