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REFERENCE LINKING PLATFORM OF KOREA S&T JOURNALS
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Biomolecules and Therapeutics
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The Korean Society of Applied Pharmacology
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Volume & Issues
Volume 13, Issue 4 - Dec 2005
Volume 13, Issue 3 - Sep 2005
Volume 13, Issue 2 - Jun 2005
Volume 13, Issue 1 - Mar 2005
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Plasma Membrane Transporters for Lead and Cadmium
Bressler, Joseph P. ; Olivi, Luisa ; Kim, Yong-Bae ; Bannon, Desmond ; Ko, Hong-Sook ; Cheong, Jae-Hoon ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 1~6
Lead and cadmium are potent environmental toxicants that affect populations living in Europe. Americas, and Asia. Identifying transporters for lead and cadmium could potentially 1 help us better understand possible risk factors. The iron transporter, divalent metal transporter 1 (DMT1), mediates intestinal transport of cadmium, and lead in yeast and fobroblasts overexpressing DMT1. In human intestinal cells knocking down expression of DMT1 attenuated uptake of cadmium and iron but not lead. A possible explanation is the expression of a second transporter for lead in intestine. In astrocytes, however, DMT1 appears to transport lead in an extracellular buffer at pH value. At neutral pH, transport was not mediated by DMT1 but rather by a transporter that is stimulated by bicarbonate and inhibited by 4,4'-diisothiocyanatodihydrostilbene-2,2'-disulfonic acid. The identity of this lead transporter will beverified by future study.
GyeongshinhaeGihwan T1 has Controlling Effects on the Factors Associated with Obesity
An, Hyo-Jin ; Choi, In-Young ; Jung, Yang-Sam ; Yoon, Ki-Hyeon ; Kim, Hyung-Min ; Hong, Seung-Heon ; Shin, Soon-Shik ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 7~12
GyeongshinhaeGihwan T1 (GGT1) is a newly developed oriental medicine to help weight control. We investigated nitric oxide production and cytokine secretion in mouse peritoneal macrophages. According to recent reports, macrophages are participated in fat accumulation and closely related with obesity. In this study, using mouse peritoneal macrophages, we have examined whether GGT1 affects the production of nitric oxide (NO), tumor necrosis factor-
), and interleukin (IL)-12 by the stimulation of interferon-
and lipopolysaccharide (LPS). GGT1 inhibits LPS-induced NO production in a dose-dependent manner. The decrease in NO synthesis was reflected as a decreased amount of inducible NO synthese protein. We also found that GGT1 inhibits pro-inflammatory cytokines, TNF-
and IL-12 production. In mouse embryo preadipocyte 3T3-L1, GGT1 reduced the viability in a dose-dependent manner. These findings suggest that GGT1 may have potential effects in preventing and controlling adipogenesis and obesity.
Inhibitory Action of the Natural Product AP1700 on the Withdrawal Syndrome of Nalbuphine
Kang, Jong-Seok ; Lee, Hun-Kyu ; Kim, Dong-Hyun ; Yoo, Hwan-Soo ; Jang, So-Yong ; Oh, Sei-Kwan ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 13~19
The study was undertaken to determine the antagonism of the AP1700 on the development of nalbuphine-induced tolerance and physical dependence. AP1700 is an oriental drug preparationcomposed of 5 natural products and is known to have antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of antinarcotic action with an oral dose of 250 mg/kg in rats. AP1700 significantly inhibits the development of nalbuphine-induced physical dependence but does not the tolerance. Mitogen-activated protein kinase, which include extracellular signal-regulated kinase (ERK), p38 and c-Jun N-terminal kinase (JNK)/stress-activated protein kinase (SAPK) play critical roles in cell growth and survival and drug abuse. The level of pCREB was elevated in the hippocampus by the chronic treatment with nalbuphine, however, the elevation of pCREB was not inhibited by the AP1700 co-treatment. Interestingly, the level of pERK was decreased in the co-treatment with nalbuphine and AP1700 on the cortex and striatum. However, the level of nNOS and NR1 was not modulated by the treatment with nalbuphine or AP1700 on the cortex, hippocampus and striatum in the rat brain. These results suggest that the AP1700 could be used to ameliorate the nalbuphine withdrawal symptoms.
Antiarrhythmic Effects of KR-32570, a Novel Na
Exchanger Inhibitor, on Ischemia/Reperfusion-Induced Arrhythmias
Hwang, Geum-Shil ; Seo, Ho-Won ; Lee, Kyu-Yang ; Lee, Sun-Kyung ; Yoo, Sung-Eun ; Lee, Byung-Ho ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 20~25
The present study was performed to evaluate antiarrhythmic effects of KR-32570, a novel inhibitor of sodium hydrogen exchanger subtype-1 (NHE-1), in rat arrhythmia induced by focal ischemia and reperfusion. During ischemia, KR-32570 significantly decreased the number of premature ventricular contraction (PVC) from 152.0 times to 75.5, 52.4 and 20.0 times for 0.1, 0.3 and 1.0 mg/kg, respectively (p<0.05) and the duration of ventricular tachycardia (VT) from 88.1 s to 35.8, 7.7 and 1.3 s, respectively(p<0.05) in anesthetized rats subjected to 10-min coronary occlusion of coronary artery. Similarlt to ischemia-induced arrhythmia, KR-32570 significantly decreased reperfusion-induced arrhythmia including PVC (41.3, 21.5, 11.3 and 6.6 times at vehicle, 0.1, 0.3 and 1.0 mg/kg, respectively, p<0.05) and VT (100.5, 64.2, 25.8 and 25.2 s, respectively, p<0.05), and VF (86.9, 27.5, 6.9 and 0 s, respectively, p<0.05). Moreover, KR-32570 dose-dependently decreased the incidence of mortality occurring after reperfusion (41, 27, 18 and 0% at vehicle, 0.1, 0.3, 1.0 mg/kg, respectively). These results suggest that KR-32570 has a potent antiarrhythmic effect in rat arrhythmia induced by ischemia and reperfusion.
Cholinomimetic Properties of a Water-Soluble Fraction from Mulberry Leaves in Rats
Lee, Ju-Seon ; Chung, Sung-Hyun ; Lee, Yong-Sup ; Jin, Chang-Bae ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 26~31
The present study examined effects of a water-soluble fraction from mulberry leaves (ML water fraction) on the circulatory and autonomic nervous systems, which were compared with those of acetylcholine (ACh) used as a reference drug in order to elucidate its mechanism of action. Intravenous administration of ACh or a ML water fraction produced temporary depressor and tachycardiac responses in a dose-dependent manner in unrestrained, conscious Sprague-Dawley rats. The systemic hemodynamic effects of ACh and a ML water fraction were almost completely blocked by pretreatment with atropine, a muscarinic antagonist. The depressor responses to ACh and a ML water fraction were slightly enhanced and prolonged by pretreatment with neostigmine, an anticholinesterase, whereas the tachycardiac responses were remarkably blocked by pretreatment with pentolinium, a ganglionic blocking agent. In vitro experiments using the ileum isolated from rats showed that ACh and a ML water fraction increased ileal contractility in a dose-dependent manner. The increases in ileal contractility were also completely abolished in the presence of atropine. Finally, the specific binding of [
]quinuclidinyl benzilate, a muscarinic antagonist, to rat cortical synaptic membranes was inhibited by a ML water fraction in a concentration-dependent manner with an IC
value of 9.5 mg/ml. The results suggest that the effects of a ML water fraction are mediated through direct stimulation of muscarinic cholinergic receptors by unknown cholinomimetic substance(s) contained in that fraction.
Isoliquiritigenin : A Competitive Tyrosinase Inhibitor from the Heartwood of Dalbergia odorifera
Kang, Tai-Hyun ; Tian, Yu-Hua ; Kim, Youn-Chul ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 32~34
Effect of isoliquiritigenin isolated from the heartwood of Dalbergia odorifera T. Chen (Leguminosae) on mushroom tyrosinase activity was investigated in vitro using L-tyrosine and L-3, 4-dihydroxyphenylalanine (L-DOPA) as the substrates. When L-tyrosine was used as a substrate, both isoliquiritigenin and kojic acid, a positive control, inhibited tyrosinase activity in a concentration-dependent manner. IC
values of isoliquiritigenin and kojic acid were 61.4 and 52.2
, respectively. However, isoliquiritigenin showed week inhibitory effect on the oxidation of L-DOPA by tyrosinase with inhibition ratio of 9.1
7.1% at 100
. It is also suggested that 3-unsubstituted and 4-hydroxyl phenyl group in isoliquiritigenin plays an important role on the inhibition of tyrosinase activity when L-tyrosine was used as a substrate. Analysis of Lineweaver-Burk plot showed that isoliquiritigenin acts as a competitive inhibitor in case of L-tyrosine as a substrate.
Effects of Adenylate Cyclase, Guanylate Cyclase and K
Channel Blockade on the Cerebral Blood Flow Response Induced by Adenosine A
Receptor Agonist in the Rats
Youn, Doo-Sang ; Shin, In-Chul ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 35~40
This study was performed to investigate the regulatory mechanism of cerebral blood flow of adenosine A
receptor agonist in the rats, and to define whether its mechanism is mediated by adenylate cyclase, guanylate cyclase and potassium channel. In pentobarbital-anesthetized, pancuronium-paralyzed and artificially ventilated male Sprague-Dawley rats, all drugs were applied topically to the cerebral cortex. Blood flow from cerebral cortex was measured using laser-Doppler flowmetry. Topical application of an adenosine A
receptor agonist, 5'-N-ethylcarboxamidoadenosine (NECA; 4 umol/I) increased cerebral blood flow. This effect of NECA (4 umol/I) was not blocked by pretreatment with adenylate cyclase inhibitor, MDL-12,330 (20 umol/I). But effect of NECA (4 umol/I) was blocked by pretreatment with guanylate cyclase inhibitor, LY-83,583 (10 umol/I) and pretreatment with ATP-sensitive potassium channel inhibitor, glipizide (5 umol/I). These results suggest that adenosine A
receptor increases cerebral blood flow. It seems that this action of adenosine A
receptor is mediated via the activation of guanylate cyclase and ATP-sensitive potassium channel in the cerebral cortex of the rats.
The Effect of Oak Wood Vinegar Extract on Blood Alcohol Concentration and Hangover Syndrome
Choi, Young-In ; Kwon, Jin-Soo ; Song, Yoon-Seok ; Wang, Sung-Ho ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 41~47
The study was conducted to determine whether oak wood vinegar extract influences blood alcohol concentration and hangover syndrome in healthy volunteers. 2% wood vinegar extract was effective to inhibit increase of blood alcohol concentration after alcohol intake and showed significantly different (P<0.1) compared to placebo. By result of questionnaire of volunteers, wood vinegar extract showed effects improving hangover syndrome. In comparative study about blood alcohol concentration and hangover syndrome of wood vinegar extract and other extract that hangover improvement effect was reported, average maximum blood alcohol concentration was lowered in those taking wood vinegar extract than those taking other extract. At drinking completion 210minutes (T210), blood alcohol concentration of those taking wood vinegar extract was the lowest by 0.063% compared with other extract but was not significantly different between in those taking wood vinegar extract and in those taking other extract. However, wood vinegar extract's experimental group was the highest by 0.462 in decrement rate of blood alcohol concentration and, when did P<0.1 by significance level, indicated difference that mean statistically compared to placebo group uniquely. At those taking wood vinegar extract, the improvement rate and the aggravation rate of hangover syndrome was each 87%, 2%. Thus it was concluded that wood vinegar extract showed excellent alcohol oxidation and was effective in hangover improvement.
Influence of Nicorandil on Aortic Strip's Contractility and Blood Pressure of the Rat
Lim, Dong-Yoon ; Kim, Yong-Jik ; Hong, Soon-Pyo ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 48~58
The present study was conducted to investigate the effects of nicorandil on arterial blood pressure and vascular contractile responses in the normotensive anesthetized rats and to establish the mechanism of action. Nicorandil (30~300
) given into a femoral vein of the normotensive anesthetized rat produced a dose-dependent depressor response. These nicorandil-induced hypotensive responses were not affected by pretreatment with atropine (3.0 mg/kg, i.v.) or propranolol (2.0 mg/kg, i.v.), while markedly inhibited in the presence of chlorisondamine (1.0 mg/kg, i.v.) or phentolamine (2.0 mg/kg, i.v.). Futhermore, after the pretreatment with 4-aminopyridine (1.0 mg/kg/30 min, i.v.) or glibenclamide (50.0
/30min) into a femoral vein made a significant reproduction in pressor responses induced by intravenous norepinephrine. In he isolated rat aortic strips, both phenylephrine (10
M)- and high potassium (5.6
M)-inducedcontractile responses were dose-dependently depressed in the presence of nicorandil (25~100
). Collectively, these experimental results demonstrate that intravenous nicorandil causes a dose-dependent depressor action in the anesthetized rat at least partly through the blockade of vascular adrenergic
-receptors, in addition to the well-known mechanism of potassium channel opening-induced vasorelaxation.
Validation of Kinetic Method for the PKA Assay in Plasma-Derived Products
Shin, In-Soo ; Hong, Choong-Man ; Koh, Hyun-Chul ; Hong, Seung-Hwa ;
Biomolecules and Therapeutics, volume 13, issue 1, 2005, Pages 59~63
A kinetic assay was carried out in order to compare the ability of detection for prekallikrein activator(PKA) in plasma-derived products with that of an endpoint assay and a commercial method. Using these methods, 9 human albumin preparations were assayed and compared to each other. The coefficient of variation between the Kinetic assay and the end point assay was found within 6.6% and this result showed that two methods were highly correlative and the end point assay could act as a replacement of the kinetic assay. Another important goal of this study was to investigate the reproducibility among laboratories on the kinetic assay. A collaborative study was performed to validate the kinetic method with intra and inter assays. The coefficient of variation for the intra assay of each laboratory was less than 4% and that for between individuals in the inter assay was 4.1%. These results revealed that the kinetic assay showed good reproducibility. The contents of PKA in plasma-derived products were also determined by the kinetic assay. As a result, it was found that trace amounts of PKA were present in 32 human immunoglobulin preparations, however the average concentration of PKA in 171 albumin preparations was 5.8 IU/mL.