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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 2, Issue 4 - Dec 1994
Volume 2, Issue 3 - Nov 1994
Volume 2, Issue 2 - Aug 1994
Volume 2, Issue 1 - Apr 1994
Selecting the target year
Production rind Characterization of the Polyclonal Anti-peptide Antibody for
Kim, Hee-Jin ; Shin, Chan-Young ; Sang Bong lee ; Ko, Kwang-Ho ;
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 303~309
The analysis of membrane receptors for hormones and neurotransmitters has progressed considerably by pharmacological and biochemical means and more recently through the use of specific antibodies. Two kinds of antibodies could be produced, one is from synthetic peptides and the other from proteins such as purified receptor. Anti-peptide antibodies gave some advantages; epitope is evident and also receptor purification in quantity is not prerequisite. It can be also applied to the study of receptor structure-activity relationship. The purpose of the present study was 1) to produce and characterize a polyclonal antibody against a synthetic
2-adrenergic receptor peptide(Phe-Gly-Asn-Phe-Trp-Cys-Phe-Trp-Thr-Ser-Ile-Asp-Val-Leu) and 2) to determine the effects of this antibody on the
-adrenergic receptor ligand interaction. The peptide sequence contains an amino acid residue such as Asp-113 which was identified as one of important component for receptor-ligand interaction in site-directed mutagenesis studies. Production of antibody was performed by immunization of rabbits through popliteal lymph node with the peptide coupled with Keyhole Limpet Hemocyanin (KLH). The titer of antibody against this peptide was 1 : 1000. The anti-peptide antibody was able to detect a 67 kDa protein band in western blot corresponding to the molecular weight of the
-adrenergic receptor in partially purified receptor fraction derived from guinea pig lung. The antisera inhibited the specific binding of [
-adrenergic receptor in a concentration-dependent manner. The results from this study suggest that the peptide sequence selected in the present study is important for the receptor ligand interaction.
Pharmacokinetics and Tissue Distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor) after Intravenous, Intramuscular or Subcutaneous Administrations to the Laboratory Animals.
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 310~315
The pharmacokinetics and tissue distribution of DA-3030 (recombinant human granulocyte colony-stimulating factor, rhG-CSF, recently manufactured by Dong-A research laboratory of Dong-A Pharmaceutical Company) were compared with reported data in the literature. After intravenous(i.v.) administration of DA-3030, at dose of 5, 10 and 100
/kg to rats, some pharmacokinetic parameters, such as terminal half-lives(1.05, 1.19 and 1.83 hr, respectively) and clearance (84.0, 54.8 and 45.5 mι/hr/kg, repectively), were dose-dependent. This could be due to the saturable metabolism of DA-3030 in rats. Similar results were also reported. After subcutaneous(s.c.) and intramuscular(i.m.) administrations of DA-3030, 10
/kg to rats, the extent of bioavailability(absolute bioavailability) were incomplete; the values were 23.3 and 18.2% after s.c. and i.m. injections, respectively, due to the degradation of DA-3030 by protease. After 7-consecutive day i.v. administrations of DA-3030, 10
/kg/day, to rats, the plasma concentrations and pharmacokinetic parameters of DA-3030 were not significantly different from those in single administration. In mice and dogs at DA-3030 dose of 10
/kg, the plasma concentrations of DA-3030 were also declined rapidly with terminal half-lives of 1.31 and 1.15 hr, respectively. DA-3030 was highly concentrated in the kidney after i.v. administration of DA-3030, 10
/kg, to rats, and the results were similar to those obtained using radiolabelled rhG-CSF in the literature. Above data indicate that DA-3030 has similar properties to rhG-CSF manufactured by other companies in view of pharmacokinetics.
Effect of Ginseng Total Saponin on the Development of Psychic and Physical Dependence on Nalbuphine
Kim, Hack-Seang ; Oh, Ki-Won ;
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 316~321
This study was undertaken to estimate whether nalbuphine, a mixed agonist/antagonist opioid analgesic produced psychic dependence. Moreover, the physical dependence liability of nalbuphine was compared with that of morphine after 7 days administrations of the drugs in mice and rats, and the effects of ginseng total saponin (GTS) on the development of physical dependence on nalbuphine were also studied. Nalbuphine did not produce psychic dependence. However, various abstinence signs precipitated by naloxone were observed in nalbuphine-dependent mice and rats. As the nature of the dependence syndrome produced by nalbuphine 30 mg/kg under these conditions seems similar to that induced by morphine 10 mg/kg, it is clear that nalbuphine possesses the substantial abuse potential. Therefore, nalbuphine may be needed to initiate more stringent controls for the prevention of nalbuphine abuse. On the other hand, GTS inhibited the development of physical dependence on nalbuphine and reduced the contents of dopamine and its metabolite in the brains of mice. Accordingly, results of this study suggest that the inhibitory effects of GTS on the development of physical dependence on nalbuphine may involve dopaminergic mechanism. GTS may be useful for the therapy of physical dependence on nalbuphine.
Protective Effect of CFC-101, a Pseudomonas Vaccine, in Mice
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 322~325
To optimize the immunological efficacy of CFC-101, an outer-membrane protein vaccine purified from relatively less pathogenic 4 different Pseudomonas aeruginosa strains, we investigated to establish its dose, administration route, interval and frequency of vaccination in mice. As expected, the 4 CFC-101 producing strains were less pathogenic than the challenging organism, P. aeruginosa GN11189. CFC-101 completely protected the death caused by P. aeruginosa at above 0.05 mg/kg vaccinized by 3 times with 7-day intervals. At the optimally effective dose of 0.2 mg/kg of CFC-101, at least 3 immunizations were necessary for complete protection against P. aeruginosa-induced death. If immunized 3 times, the immunization interval could be shortened up to 2 days to acquire the best protection against P. aeruginosa. CFC-101 was effective either by intraperitoneal, subcutaneous or intramuscular but not by oral administration. The present results show that the newly developed Pseudomonas vaccine, CFC-101, is highly effective for the protection from death caused by pseudomonal infections.
Active and Passive Protective Effect of CFC-101 (Pseudomonas Vaccine) in Mice
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 326~330
The treatment of pseudomonal infection is a perplexed problem because of its modest susceptibility to most of the major antibiotics. A novel Pseudomonas vaccine(CFC-101) was prepared from the outer membrane protein fractions of several Pseudomonas strains. In this study, we examined CFC-101's effectiveness in both active and passive immunization models. CFC-101 in mice at 0.2 mg/kg, i.p., given three times at two-day intervals, completely prevented the death caused by Pseudomonas aeruginosa. Antibody titer, in accordance with the protective effect in this active immunization, was elevated to its peak level following three consecutive administrations of CFC-101. Thereafter, antibody titer stayed at a constantly high level. Each outer membrane protein fraction from the four CFC-101 producers, exhibited good cross-protective effects in mouse infection models against different Fisher types of P. aeruginosa. In the passive immunization model, 21~336
/kg of anti-rabbit IgG to CFC-101, when mice being infected with a challenge strain, prevented the Pseudomonhas-induced death up to 60%. Therefore, the preventive effect of CFC-101 was verified in both the active and passive immunization models.
Antigenicity of CFC-101(Pseudomonas vaccine) in Guinea Pigs and Mice
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 331~335
As a part of the safety evaluation of Pseudomonas vaccine(CFC-101), antigenicity tests were carried out in guinea pigs and mice. In active systemic anaphylaxis(ASA) test, guinea pigs showed no sign or only moderate sign(1/5) when sensitized and challenged with up to 200
/kg. In homologous passive cutaneous anaphylaxis(PCA) test using guinea pigs, inoculation of CFC-101 alone did not produce CFC-101-specific antibody. When inoculated with 200
/kg plus adjuvant, challenge of 200
/kg produced PCA titer of 32(5/5) but challenge of 20
/kg did not produce CFC-101-specific antibody. In heterologous PCA test using mice, CFC-101-specific antibody was not detected when sensitized with CFC-101 alone. Some animals(3/12) showed positive PCA response when inoculated with 200
/kg plus alum. In passive hemagglutination (PHA) test, although no antibody was detected at 20
/kg, inoculation of 200
/kg alone or with alum produced positive response in all animals. This result has already been predicted because CFC-101 is a vaccine developed for the purpose of immunization. From the above results, it can be concluded that there is no adverse antigenic potential up to 10 times clinical dose of 200
General Pharmacology of Erythropoietin Produced by a New Recombinant DNA Technique
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 336~342
The general pharmacological properties of EPO were investigated in various animals administering intravenously and in vitro system. The results were as follows. 1. Central nervous system: EPO at doses of 70, 700, 7000 U/kg showed no effect In mice on general behavior, on strychnine- and pentetrazol-induced convulsion and on acetic acid-induced writhing syndrome. The hexobarbital-induced sleeping time in mice was slightly reduced by EPO at a dose of 7000 U/kg but did not change at doses of 70, 700 U/kg. The body temperature in rats was slightly decreased by EPO at doses of 700, 7,000 U/kg but the change was in normal physiological range. 2. Respiratory and cardiovascular system: EPO showed no effect on respiratory rate, blood pressure, heart rate, femoral blood flow, and electrocardiogram in anesthetized dogs at doses of 70, 700, 7000 U/kg. 3. Smooth muscle: EPO at concentrations of 70, 700 U/ml had no effect on the contractile response of isolated guinea pig ileum to histamine and acetylcholine. 4. Water and electrolytes excretion: EPO at dose above 700 U/kg increased urine volume in rats but did not affect the concentrations of
in urine. 5. Gastrointestinal system: EPO(70, 700, 7000 U/kg) had no effect on the intestinal charcoal meal propulsion 6. Blood coagulation system: The administration of EPO(70, 700, 7000 U/kg) had no effect on the plasma prothrombin time(PT) and activated partial thromboplastin time(APTT) in mice. Platelet aggregation induced by ADP and collagen was not influenced by EPO(70 U/ml, 700 U/ml). The overall results obtained indicated that EPO exerts almost no serious pharmacological effect even at a 100-fold clinical dose(7000 U/kg).
Efficacy of Recombinant Erythropoietin from CHO Cells
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 343~346
In vivo activity of recombinant human erythropoietin (rh-EPO) has been examined using polycythemic model in mice and acute hemorrhage model in rats. The number of reticulocytes in blood stream was increased after a single injection of rh-EPO depending on the dosage of rh-EPO in polycythemy model. It seemed that optimal dose of rh-EPO for polycythemic mice was around 1-10 U/kg. Rh-EPO also showed the effectiveness for increase of reticulocyte numbers both in male and female rats after bleeding. The number of reticulocytes and the change of hemoglobin concentration in the blood stream of normal rats has been examined after injection of rh-EPO. The maximum value of reticulocyte was observed on the 6th day of the injection in these normal rats. In addition, the increase of reticulocyte and the concentration of hemoglobin were dependent on the dosage of rh-EPO. The increase of hemoglobin concentration was continued to the 9th day after injection. In this study, the efficacy of rh-EPO was confirmed in both mice and rats.
General Pharmacology of DWP 301, a New Combined Drug for Gastroduodenal Diseases
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 347~360
The general and some pharmacological actions of DWP 301 were investigated in animals and the following results were obtained. In central nervous system, DWP 301 had no effects on the pentobarbital induced anaesthesia, rotarod test, traction test, analgesic action, anticonvulsant action in mice and body temperature in rat. But DWP 301 showed a little decrease of locomotor activity at a dose of 3,000 mg/kg. From these results, DWP 301 was considered to have little pharmacological effect on the central nervous system. Furthermore, DWP 301 had no influences on the normal blood pressure and heart rate. DWP 301 showed no effect on the isolated guinea pig ileum, trachea, right atrium, and nonpregnant rat uterus. But, in the isolated guinea pig vas deference, DWP 301 had showed inhibitory effect on the contractions produced by norepinephrine. DWP 301 showed rise of gastric juice pH and decrease of urine volume. Also, DWP 301 had no effect on the gastrointestinal motility and blood aggregation. From these results, it is concluded that the general pharmacological effect of DWP 301 are similar to or weaker than M and AGA.
Properties of Muscarinic Receptor in Bovine Adrenal Medulla
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 361~368
The nature of the muscarinic receptors in bovine adrenal medulla was investigated in this study. [
H]Quinuclidinyl benzilate(QNB) specifically bound to a single class of muscarinic receptor with a
value of about 70 pM in bovine adrenal medullary, cardiac ventricular and ileal homogenates. Pirenzepine inhibition curves of [
H]QNB binding to cardiac ventricular and ileal homogenates were steep, indicating the presence of a single class of binding site for pirenzepine with a Ki value of 990 nM and 508 nM, respectively. However, pirenzepine/[
H]QNB competition binding curves in adrenal medulla suggested the presence of two binding sites (Hill coefficient=0.59) with a high(
) and a low(
) affinity. Respective Ki values for pirenfepine were 16 nM and 633 nM, with 44% of total sites having a high affinity(
). Gallamine, which is selective to cardiac
-receptor, inhibited [
H]QNB binding to adrenal medullary, cardiac ventricular and ileal homogenates with Ki values of 12
M and 13
M, respectively. Thus, the binding affinities of pirenzepine and gallamine for
-receptor in adrenal medulla were similar to those in ileum, which contains the
-receptor. These results indicate that the
- muscarinic receptor subtypes coexist in the bovine adrenal medulla.a.
General Pharmacology of G009, a Polysaccharide Isolated from Ganoderma lucidum IY 009
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 369~375
A polysaccharide, G009, isolated from Ganoderma lucidum IY 009, was subjected to investigating on general pharmacology. This material at the large oral doses of 1000 and 2000 mg/kg in mice did not exhibit any abnormal behaviors and another effects on central nervous system. It also had no influences on hexobarbital-induced sleeping time, rotarod test and spontaneous activity test at each oral dose of 1000 mg/kg in mice. No effects on the body temperature and on acetic acid induced writhing syndrome in mice were observed with its oral administration at 1000 mg/kg, and the convulsions induced by strychnine and pentetrazole were not inhibited at its oral doses of 1000 mg/kg in mice. The solution of G009 as given intravenously at the doses of 30 and 60 mg/kg in rabbit had no influences on blood pressure and respiration rates and depth. In isolated organs of rat uterus and fundus muscles and guineapig ileum and trachea, it did not show any contraction or relaxation at the concentrations of 2
g/ml, and the contractive actions produced by oxytocin, acetylcholine, serotonin and histamine were not inhibited at the same doses. This material showed no effect on intestinal propulsion test in mice and gastric secretion in rats at the oral doses of 1000 mg/kg. However, it is interesting that the material exhibited potent inhibition of acidified aspirin induced gastric damage at the doses of 500 and 1000 mg/kg in rats.
Effects of the Polysaccharides from Irpex lacteus Fr. on some Characteristic Immune Responses in the Polyclonal Activation Induced with Mercuric Chloride in CBA Female Mice
Biomolecules and Therapeutics, volume 2, issue 4, 1994, Pages 376~382
Repeated injections of low-doses of mercuric chloride in rats or mice induce polyclonal activation which includes the induction of anti-glomerular basement membrane (GBM) antibodies and circulating immune complex and it results in nephritis. Because this disease is autoimmune mediated disease resulted from immune dysfunction, immunomodulators are used to control the symptoms or to cure the disease. Irpex lacteus Fr. is a kind of new medicinal fungus. The polysaccharide fraction extracted from submerged fermentation of Irpex lacteus Fr. decreased the serum agglutinin, serolysin and IgM plaque forming cells in normal mice. The hitherto obtained clinical results suggested that it significantly improved the oligourea, edema, and hypertension in patients who have nephritis. To elucidate the action-mechanisms of Irpex lacteus Fr., we established the experimental model of HgCl
induced polyclonal activation by intraperitoneal administrations of HgCl
to mice. To assess the immunomodulating effect of Irpex lacteus fraction, we Investigated its effects on the mitogen induced proliferation and IgM PFC counts of splenic lymphocytes in mice during the treatment of HgCl
. The Irpex lacteus polysaccharide reduced the abnormally increased mitogen induced Iymphocyte proliferation and IgM PFCs to almost normal levels. And the Irpex lacteus polysaccharides prevented the increasement of serum immunoglobulin level induced by HgCl
. These data suggested that the Irpex lacteus polysaccharides might have the immunomodulating activity to prevent and /or improve the HgCl
induced autoimmune disease.