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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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Journal DOI :
The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 7, Issue 4 - Dec 1999
Volume 7, Issue 3 - Sep 1999
Volume 7, Issue 2 - Jun 1999
Volume 7, Issue 1 - Mar 1999
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Functional Properties of Human Muscarinic Receptors Hm1, Hm2 and Hm3 Expressed in a Baculovirus/Sf9 Cell System
Woo, Hyun-Ae ; Woo, Yae-Bong ; Bae, Seung-Jin ; Kim, Hwa-Jung ;
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 307~314
The human muscarinic acetylcholine receptor (mAChR) subtypes Hml, Hm2 and Hm3 have been expressed in insect cells (Spodoptera frugiperda, Sf9) using the baculovirus expression system. Expression of relevant DNA, transcript and receptor proteins was identified by PCR, Northern blotting and [
]QNB binding, respectively. As assessed by [
]QNB binding sites, yields of muscarinic receptors in membrane preparations in this study were as about 5-20 times high as those in mammalian cells reported in previous studies. The [
]QNB competition binding studies with well-known subtype-selective mAChR antagonists showed that the receptors expressed in Sf9 cells retain the pharmacological characteristics expected for the ml , m2 and m3 muscarinic receptors. The ml-selective antagonist, pirenzepine, displayed a considerably higher affinity for Hml by 110-fold and 35-fold than for Hm2 and Hm3, respectively, The m2-selective methoctramine displayed a significantly higher affinity for Hm2 than for Hml and Hm3 (10- and 26-fold, respectively). p-F-HHSiD exhibited high affinity for Hm3 that is not significantly different from those for Hml, but 66-fold higher than its affinity for Hm2. The functional coupling of the recombinant receptors to second messenger systems was also examined. While both Hml and Hm3 stimulated phosphoinositide hydrolysis upon activation by carba-chol, Hm2 produced no response. On the other hand, activation of mAChRs induced the inhibition of forsko-lin-stimulated cyclic AMP formation in Hm2-expressing cells, whereas the significant dose-dependent increase in or poor response on cyclic AMP formation were produced in Hml or Hm3-expressing cells, respectively. These results indicate the differential coupling of recombinant Hml, Hm2 and Hm3 receptors expressed in SF9 cells to intracellular signalling system.
Inhibition of TCDD Induced Cyplal Expression by SNP In Hepa I Cells
Kim, Ji-E. ; Sheen, Yhun-Y. ;
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 315~321
Since it has been known that hypoxia increases inducible nitric oxide synthase (iNOS) gene expression through hypoxia responsive element, it was possible to establish the hypothesis that nitric oxide could be a mediator of hypoxia to inhibit Cyplal promoter activity. In order to test this hypothesis, we have undertaken the study to examine the effects of hypoxia and nitric oxide on Cyplal promoter activity in Hepa I cells. Mouse Cyplal 5'flanking DNA, 1.6 Kb was cloned into pGL3 expression vector in order to construct pmCyplal-Luc. Hepa I cells were transfected with pmCyplal-Luc and were treated with
M TCDD and nitric oxide producing agents, such as lipopolysaccharide(LPS), sodium nitroprusside (SNP). Luciferase activity of reporter gene was measured from pmCyplal-Luc transfected Hepa I cell lysate which contains 2 g total protein using luciferin as a substrate. Nitric oxide producing agents, such as lipopolysaccharide (LPS), sodium nitroprusside(SNP) showed inhibition of luciferase activity that was induced by
M TCDD treatment with dose dependent manner. Concomitant treatment of 1mM
M sodium nitro-prusside recovered luciferase activity from the TCDD induced luciferase activity that was inhibited by nitric oxide producing agents. These demonstrated that nitric oxide could be a mediator of inhibitors on dioxin induced Cyplal expression in Hepa I cells.
Relationship between the Changes of Catecholamines and Blood Pressure Induced by Exposure to Low- and High-levels of Lead in Rats
Yoon, Suh-Young ; Yoo, Kyeong-Seok ; Cheong, Jae-Hoon ;
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 322~328
In this study, it was tested whether the changes of catecholamines and its metabolites are related with the changes of blood pressure(BP) induced by different levels of lead exposure. Adult male SD rats were exposed to lead by giving drinking water containing 50(low doses), 200 and 1,000 ppm(high doses) of lead(as lead acetate) or sodium acetate(for control groups, supplying an identical amount of acetate) for 7 or 16 weeks. The systolic BP was measured in the unanesthetized state by the tail-cuff technique. Levels of catecholamines and its metabolites in urine were measured by HPLC-ECD. Rats receiving 200 and 1,000 ppm developed an elevation of systolic BP at 3 and 7 weeks compared with week 0, but blood pressure levels at 16 weeks returned to normal. For the 50 ppm lead treated group, systolic BP increased significantly at 7 weeks and 16 weeks. The concentrations of norepinephrine and VMA in the urine of lead exposed rats changed similarly to the changes of blood pressure, but blood viscosity levels in all lead treated rats increased continuously during all lead treatment periods. This result suggests that the changes of catecholamines and its metabolites in urine by lead intoxication may influence the changes of blood pressure.
Signal Transduction in the Osteoblast Cells
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 329~334
Recently, cellular signal transduction mechanisms are greatly understood. However, bone cell signaling is not completely characterized. Interestingly, bone cells synthesize a number of growth factors such as IGF-I PDGF, IGF-II etc., suggesting these growth factors play important roles in bone cell signaling. In the present study, potential roles of nitric oxide (NO) and protein kinases in osteoblast signal transduction are proposed.
Blood Glucose Lowering Activity and Mechanism of Supungsungihyan (SPSGH) in db/db Mouse
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 335~341
Antidiabetic activity and mechanism of Supungsungihyan(SPSGH) were examined in db/db mice, which is a spontaneously hyperglycemic, hyperinsulinemic and obese animal model. SPSGH and acarbose were administered orally for 4 weeks. Fasting and non-fasting serum glucose, glycated hemoglobin and trig-lyceride of SPSGH treated group were all reduced when compared with those of db/db control group. At 12th week after birth, SPSGH increased an insulin secretion although statistic significance was not seen. Total activities of sucrose, maltase and lactase in SPSGH treated group were not significantly different from those in db/db control. On the other hand, sucrase and maltase activities in acarbose treated groups were increased. Effect of SPSGH on mRNA expression of glucose transporter(GLUT-4) was also examined by RT-PCR and in vitro transcription with co-amplification of rat
-actin gene as an internal standard. Muscular GLUT-4 mRNA expression in SPSGH treated group was increased significantly. These results may suggest that SPSGH lowered blood glucose ascribing to upregulation of muscular GLUT-4 mRNA expression.
Effects of Cyclosporine on Glucose Tolerance and Insulin Sensitivity in Sprague-Dawley Rats
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 342~346
This study was performed to investigate the effect of cyclosporine (CsA) on glucose tolerance and peripheral insulin sensitivity in normal Sprague-Dawley rats. After daily treament of CsA (10 mg/kg, i.p.) for two weeks, glucose tolerance tests were carried out by the treatment of glucose (Glu, 2 g/kg, i.p.) alone or in conjunction with exogenous insulin (Ins; human regular insulin, 5 U/kg, s.c.) and measured the decrement of area under the time-plasma glucose concentration curve (
; g.min/ml) by the trapezoidal rule. The rats were divided into three groups (Glu- (Control), Ins+Glu- and CsA+Ins+Glu-, n=7 in each group). The
of the CsA+Ins+Glu-group was significantly (p<0.01) lower than that of Glu-group (61.0% of control) and significantly (p<0.05) higher than that of Ins+Glu-group (197.4% of Ins+Glu-). The CsA+Ins+Glu- grou showed higher levels of maximal blood glucose concentration and higher
than those of Ins+Glu-group in normal rats. Besides direct pancreatic toxicity of CsA previously reported (Hahn et al., 1972), these results suggest that CsA also make the possibility to induce peripheral insulin insensitivity and glucose intolerance in normal rats.
Effect of Sodium Hyaluronate on Osteoarthrosis in Rabbit Model
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 347~353
Osteoarthrosis was induced in rabbit knees through resecton of anterior cruciate ligament. Sodium hyaluronate (1%) was administerated into articular space at the dose levels of 0.1 mg/kg once a week using 1ml sylinge and 26G needle for test groups. Saline was administrated for control groups. After 6 and 12 weeks, animals were sacrificed to conduct macroscopic observation and histopathologic examination. The articular lesions were evaluated and test groups were compared with control groups. No significant differencies were showed between test groups and control groups at macroscopic observation in both 6- and 12- week groups. In histopathologic examination, control groups showed higher osteoarthrosis than test groups. The articular surfaces of control groups showed fibrillation, denudation, pannus formation and hypocellularity. The articular surfaces of test groups showed fibrillaton and hypercellularity. These indicate that sodium hyaluronate has inhibitory effects on osteoarthrosis at least in rabbit and could be used for treatment of osteoarthrosis.
Effect of Tauroursodeoxycholic Acid on Ischemia/Reperfusion Injury in Isolated Rat Heart
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 354~361
In this study, the effects of tauroursodeoxycholic acid (TUDCA) on ischemia/ reperfusion injury were investigated on isolated heart perfusion models. Hezrts were perfused with oxygenated Krebs-henseleit solution (pH 7.4,
) on a Langendorff apparatus. After equilibration, isolated hearts were treated with TUDCA 100 and 200
or vehicle (0.02% DMSO) for 10 min before the onset of ischemia in single treatment group. In 7 day pretreatment group. TUDCA 50, 100 and 200 mg/kg body weight were given orally for 7 days before operation. After global ischemia (30 min), ischemic hearts were reperfused for 30 min. The physiological (i.e. heart rate, left ventricdular developed pressure, coronary flow, double product, time to contracture formation) and biochemical (lactate dehydrogenase; LDH) parameters were evaluated. In vehicle-treated group, time to contracture formation was 810 sec during ischemia, LVDP was 34.0 mmHg at the endpoint of reperfusion and LDH activity in total reperfusion effluent was 34.3 U/L. Single treatment with TUDCA did not change the postischemic recovery of cardiac function, LDH and time to contractur compared with ischemic control group. TUDCA pretreatment showed the tendency to decrease LDH release and to increase time to contracture and coronary flow. Our findings suggest that TUDCA does not ameliorate ischemia/reperfusion-reduced myocardial damage.
Antigastritic and Antiulcer action of Effective Compounds from Propolis Extract
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 362~370
Propolis, a natural resinous compound collected from honey bees, contains many biochemical constituents(wax, flavonoids, phenolic compounds, etc.) and has been used in traditional medicines as early as 300 B.C. It was been demonstrated that ethanol, acetylsalicylic acid, ischemia reperfusion, non-steroidal antiin-flammatory drugs and stress induce gastric lesions by promoting the generation of reactive oxygen metabolites. Therefore, some drugs that are capable of scavenging or inhibiting the generation of reactive oxygen radicals might be expected to prevent the gastric mucosal injury. The aim of this study was 1) to examine the antiulcer effect of propolis, 2) to investigate the mechanism of action by determining gastric acid secretion, lipid per-oxidation, mucus content and proton pump (
-ATPase) activity on gastric mucus in varios experimental models, and finally, 3) to isolate and identify the pure compounds that exert antiulcer activity. Step 2-1 and 2-3 sub-sub fraction shoed a significant reduction of severity of gastirc damage at the dose of 25 mg/kg in various experimental models. We isolated 4 sub-sub-sub fractions by flash column chromatography of Step 2-1 sub-sub fraction and one sub-sub-sub fraction by recrystalization of Step 2-3 sub-sub fraction. The protective effects of propolis sub-sub-sub fraction manifested sifnificant effects in HCl-ethanol induced gastric erosion model and aspirin induced gastric ulcer model. These results showed that the gastric mucosal protective effect of propolis might result from the increase of mucus secretion, free radical scavenging effect as well as the reduction of acid secretion in accordance with the reduction of
-ATPase activitv. Three compounds were isolated and identified from sub-sub fraction of propolis which showed antiulcer effects. Subsequently, these compounds were identified as a flavonoid, namely, 2-acetoxy-5,7,-dihydroxy-flavanone, galangin and chrysin.
Cytotoxicity of the Components of Albizzia julibrissin
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 371~376
By cytotoxicity screening of the 65 Korean medicinal plants against leukemia L1210 and P388D
cell line using the MTT assay in vitro, Albizzia julibrissin was studied. This plant was extracted with MeOH and MeOH extract was solvent-fractionated with CHCl
, EtOAc and n-BuOH in sequence. Each fraction by various solvents system was purified by column chromatography and preparative TLC, and four compounds were isolated. The structure of each compound was deduced from UV, IR,
C-NMR and CI-MS spectral data. The cytotoxic activity (
/_ of the compounds, quercetin-3-rhamnoside, 4',5,7-trihydroxyfla-van-3-glucoside, spinasterol-3-glucoside and acacic acid lactone, were evaluated as 5
/ml against L1210 and as 9
/ml and 0.9
/ml against P388D
Immunomodulating Activity of Alginate
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 377~384
Alginates are polysaccharides with gel-forming properties composed of 1,4-linked
-D-mannuronic acid (M),
-L-guluronic acid (G), and alternating (MG) blocks. The M-and the MG-blocks, but not the G-blocks, have been known to be the active components of the alginates in experimental models. In this study, we have examined the ability of high M-alginate to activate immune cells. Alginate induced the macrophage anti-viral activity and the lymphocyte blastogenesis, and enhanced cytotoxicity of natural killer cell. In addition, alginates stimulated the macrophages to induce the production of
, whereas alginates had no effect on NO production and suppressed the production of TNF-
. These findings suggest that high M-alginate may be modulating various elements of the host immune response.
Inhibitory Activity of Bacillus licheniformis AJ on the Growth of Diarrheal Pathogens
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 385~389
The injibitory effect of Bacillus licheniformis AJ isolated from genitourinary normal flora as a new probiotics on the growth of diarrheal pathogens was studied. This B. licheniformis AJ inhibited the growth of E.coli O-157. Salmonella typhi and Shigella sonnei as well as the infectivity of rotavirus. However, it did not inhibit the growth of Helicobacter pyloriand human intestinal bacteria although it inhibited the harmful enzyme activity of human intestinal bacteria. B. licheniformis AJ seems to excret heat-lable growth-inhibitory protein, bacteriocin, into the media. These results suggest that B. lichenoformis AJ could be used as a new type of probiotics.
General Pharmacology of CJ-50005 (Hepatitis A Vaccine)
Biomolecules and Therapeutics, volume 7, issue 4, 1999, Pages 390~396
CJ-50005 is a hepatitis A vaccine which is prepared by formalin inactivation of the HM175 virus cultured in human diploid MRC-5 cells. The general pharmacological properties of CJ-50005 were evaluated in various animals and in vitor system. CJ-50005 at the doses of 0.025, 0.25 and 0.75
/kg, i.m. had no effect on general behavior in mice, chemo- and electro-convulsions in mice, writhing syndrome induced by acetic acid in mice, the barbital sleeping time in mice, body temperature in rats, charcoal meal propulsion in mice and urine and electrolytes excretion in rats. In anesthetized dogs, CJ-50005(0.25 and 0.75
/kg, i.v) did not alter the respiratory rate, blood pressure, heart rate, femoral blood flow and ECG. In in vitro experiment, CJ-50005 at the concentration up to 0.02
/ml did not produce any changes in the contractions of the isolated ileum of guinea pigs caused by acetylcholine, histamine or
. Since these pharmacological effects of CJ-50005 were observed at dose much greater than those in clinical use (approximately 0.025
/kg, i.m.), it is likely that this vaccine may be relatively free of undesirable effects in clinical practice.