The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 53, Issue 1
Displaying 1-15 of 15 articles from this issue
  • Yasuhiro HAYASHI, Satomi HIRAI, Hisashi HARAYAMA, Terumi SAITO, Atsush ...
    1990 Volume 53 Issue 1 Pages 1-9
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The rate of proliferation of porcine aortic endothelial cells (PAEC) in response to fibroblast growth factor (FGF) was largely retarded when incubated in Dulbecco's modified Eagle's medium (DMEM) supplemented with either 1% fetal bovine serum (FBS) or 10% dialyzed FBS in place of 10% FBS. Proliferation of endothelial cells in low serum media in response to FGF was enhanced to the level of media containing FGF plus 10% FBS by the addition of the dialyzable fraction from bovine brain homogenates. From the bovine brain dialyzable fraction, two active components were purified and identified as hypoxanthine and inosine. Either hypoxanthine or inosine, at a dose of 5 μM in DMEM with 1% FBS, maximally increased the incorporation of [3H]thymidine into DNA of PAEC in low serum media in the presence of FGF. However, no additive effect was observed when hypoxanthine and inosine were added simultaneously. The present data indicate that the proliferative action of FGF on PAEC can be potentiated by hypoxanthine and inosine.
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  • Hiroyuki OHTA, Masako NISHIZUKA, Yasumasa ARAI, Hiroshi SAITO
    1990 Volume 53 Issue 1 Pages 11-18
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    Effect of short-term exposure to nerve growth factor (NGF) on neuron survival of superior cervical ganglion (SCG) transplanted into the third ventricle in rats and that on neurite outgrowth of SCG neurons in a tissue culture system were examined. Because SCG taken from 3 week-old rats exhibited a high survival rate in transplantation and they were highly sensitive to NGF in culture, they were used in the short-term NGF treatment experiment. SCG from 3 week-old rats were preincubated with NGF for 30 min at room temperature, and then they were cultured for 2 days or grafted for 14 days. Short-term exposure to NGF at the concentration of 10 μg/ml enhanced the survival of transplanted SCG neurons. The same concentration of NGF enhanced neurite outgrowth of SCG neurons in culture. These results suggest that short-term NGF pretreatment could increase the efficiency of neuronal transplantation.
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  • Kimio KARIYA, Yasuhiro MIKI, Yukiko TSURUOKA, Satoko KITANO, Eibai LEE
    1990 Volume 53 Issue 1 Pages 19-23
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The activity of peroxidases and the level of myeloperoxidase in the bone marrow of spontaneously hypertensive rats (SHR) and stroke-prone SHR (SHRSP) were determined in comparison with normotensive Wistar Kyoto rats (WKY). In the cetyltrimethylammonium bromide extract of bone marrow, the peroxidase activities using guaiacol or Kl as the electron donor of male and female WKY were different from those of SHR and SHR-SP. The peroxidase activity was also separately determined as myeloperoxidase and eosinophil peroxidase by the use of ion-exchange high pressure liquid chromatography. In males, SHR and SHR-SP contained a low activity of eosinophil peroxidase compared with WKY. Bone marrows of female SHR and SHR-SP contained a lower activity of myeloperoxidase, while SHR and SHR-SP possessed a higher activity of eosinophil peroxidase compared with WKY. No change of the level of myeloperoxidase in the bone marrow was observed among male animals. A significant decrease in the level of myeloperoxidase was observed in female SHR and SHR-SP. Therefore, these results indicate that the change in the activity of the peroxidases in the bone marrow is accompanied by the spontaneously hypertensive state.
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  • Buichi FUJITANI, Korekiyo WAKITANI
    1990 Volume 53 Issue 1 Pages 25-33
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The mechanism for the inhibition of platelet functions by a prostaglandin I2 analog, OP-41483, was studied with guinea pig platelets. OP-41483, and PGI2 as well, inhibited aggregation, ADP release and thromboxane formation of platelets with IC50 values of 4.3-5.8 ng/ml and 0.6-0.9 ng/ml, respectively. The ligand binding study using [3H]-OP-41 483 suggested that OP-41 483 bound with different affinities to two classes of bindig sites on platelets. The dissociation constant of OP-41483 for the higher affinity site corresponded to the IC50 values of its antiplatelet effect. PGI2 as well as OP-41483 displaced [3H]-OP-41483 previously bound to platelets, thus indicating that both agents exerted their antiplatelet effects by binding to the same site on platelets. OP-41483 and PGI2 activated adenylate cyclase and raised cyclic AMP levels in platelets. However, their inhibitory effect on platelet aggregation was not fully antagonized by an adenylate cyclase inhibitor, 2', 5'-dideoxyadenosine (DDA), at a concentration completely inhibiting the increase of cyclic AMP. Moreover, this DDA-resistant effect of OP-41483 disappeared in the presence of calcium chloride (10-4-10-3 M). OP-41483 and PGI2 inhibited thrombin-induced Ca++ influx into platelets. The inhibition of Ca++ influx was not reversed by DDA. Based on these results, we speculate that the inhibitory effects of OP-41483 and PGI2 on platelet functions are produced through dual mechanisms: one mediated by activation of adenylate cyclase and the other by an inhibition of Ca++ influx; and these two mechanisms seem to be independent of each other.
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  • Fumiaki ISHIDA, Yuri IIZUKA, Kyoko KAKUBARI, Yutaka KURAHASHI, Yoshio ...
    1990 Volume 53 Issue 1 Pages 35-45
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The effects of Simvastatin (MK-733), an inhibitor of 3-hydroxy-3methylglutaryl CoA (HMG-CoA) reductase, on fecal and biliary excretion of sterols and bile acids were examined using rabbits. Multiple doses of MK-733 (10 mg/ kg/day) for 7 days were found to increase fecal concentrations of neutral sterols in cholesterol-fed rabbits, but not to affect those of bile acids. Multiple doses of cholestyramine (750 mg/kg/day), a bile acid sequestrant, for 7 days increased fecal concentrations of neutral sterols and bile acids in normally fed and cholesterol-fed groups. MK-733 did not affect biliary neutral sterols and total bile acids in normally fed and cholesterol-fed groups. Cholestyramine decreased biliary concentrations of neutral sterols in both diet groups. Cholestyramine altered fecal and biliary composition of bile acids, but MK-733 did not. It was considered that MK-733 inhibited the absorption of cholesterol, resulting in an increase of the fecal concentration of neutral sterols in cholesterol-fed rabbits. The mechanism of action of MK-733 in the inhibition of cholesterol absorption is considered to be clearly different from that of cholestyramine. These results confirmed the conclusion in the previous experiment.
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  • Yoshio GOSHIMA, Shinichi NAKAMURA, Yoshimi MISU
    1990 Volume 53 Issue 1 Pages 47-56
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    In rat hypothalamic slices, L-aromatic amino acid decarboxylase (AADC) was assayed, and the actions of L-DOPA on impulse (2 Hz)-evoked norepinephrine (NE) and dopamine (DA) release were studied under inhibition of AADC. Slices were incubated with L-DOPA, and DA and NE produced by conversion of the precursor were analyzed by high performance liquid chromatography with electrochemical detection (HPLC-ECD). In the slices, the Km and Vmax of AADC were 131 μM and 122 pmol/min/mg protein, respectively. NSD-1015, an AADC inhibitor, caused a noncompetitive type of inhibition, and the Ki value was 0.086 μM. In the presence of 20 μM NSD-101 5, which was expected to cause 99.6% inhibition of AADC, L-DOPA (0.01-100 nM) concentration-dependently facilitated the release of NE from the superfused slices, and the L-DOPA (10 nM)-induced facilitation was antagonized by 100 nM ICI 89, 406 and 100 nM ICI 118, 551, a selective β1- and β2-adrenoceptor antagonist, respectively. This action of L-DOPA was not modified by 30 μM tropolone, an inhibitor of catechol-0-methyl-transferase. L-DOPA at 0.01-1 nM similarly facilitated the release of DA. A quantitative analysis revealed that the L-DOPA-induced increase in NE and DA release was much higher by a factor of 3 to 4 ordres than was the amount of DA and NE converted from L-DOPA. These results add further support to the hypothesis that L-DOPA itself acts as a neuroactive substance in the rat central nervous system.
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  • Masao HISADOME, Tetsuko FUKUDA, Michio TERASAWA
    1990 Volume 53 Issue 1 Pages 57-66
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    L-Cysteine ethylester hydrochloride (Cystanin®, ethylcysteine) at doses of 3-30 mg/kg, p.o., potentiated the reduction of nitroblue tetrazolium (NBT) by mouse peritoneal macrophages ex vivo. In in vitro experiments, this drug (30 μM) augmented NBT reduction of mouse peritoneal macrophages induced by opsonized zymosan (OZ). At the same concentration, this drug accelerated the enhancement of the OZ-induced NBT reduction by the addition of concanavalin A, N-formyl-L-methionyl-L-leucyl-L-phenylalanine or phorbol myristate acetate. This enhancing effect of ethylcysteine was completely diminished by the addition of SOD, sodium azide and catalase. In ex vivo experiments, the OZ-induced chemiluminescence of rat peritoneal macrophages and white blood cells was enhanced by the administration of ethylcysteine at doses of 3-10 mg/kg (i.p.) and 3-30 mg/kg (p.o.). In addition, this drug significantly enhanced the lumisphere-induced chemiluminescence of rat peritoneal leukocytes at 30 mg/kg (i.p.), but not the OZ-induced chemiluminescence. In in vitro experiments, this drug (30 μM) did not enhance the OZ-induced chemiluminescence response of rat peritoneal macrophages. These results suggest that ethylcysteine may enhance the intracellular generation of antimicrobial oxidants in macrophages and leukocytes.
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  • Koji TAKEUCHI, Hiromichi NIIDA, Yusuke TAKINAMI, Susumu OKABE
    1990 Volume 53 Issue 1 Pages 67-74
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    Possible involvement of increased mucosal permeability in the stimulation by prostaglandin E2 (PGE2) of duodenal HCO3- secretion was investigated in rats. PGE2 (0.3, 1 mg/kg, s.c.) dose-dependently increased HCO3- secretion in the duodenum with a significant elevation of transmucosal potential difference (PD); the PD was increased from -4.5 ± 0.3 mV to -10.0 ± 1.5 mV (mucosa negative) at 1 mg/kg. These responses caused by PGE2 were abolished by sacrificing the animals with saturated KCl (i.v.). Although a significant increase of HC03-output was observed after exposure of the mucosa to 1 M NaCl (0.5 ml), this response was accompanied by a significant reduction of PD and was not abolished after KCl injection. The mucosal permeability determined by Evans blue (1%, i.v.) was not affected by PGE2, while 1 M NaCl markedly elevated the amount of extravasated dye in both the luminal content and the mucosa. Stimulation of HC03-output by PGE2 was significantly mitigated by ouabain (3 mg/kg, s.c.) or prior exposure of the mucosa to 1 M NaCl. These results suggest that stimulation by PGE2 of duodenal HCO3- secretion is not simply due to the increased mucosal permeability, but depends rather on both the Na/K ATPase activity and the intact perfusion of the organ. The HCO3- response as induced by 1 M NaCl may result from the increased permeability and is accompanied by a marked reduction of PD.
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  • Miwa MISAWA, Shu-Chun HUANG
    1990 Volume 53 Issue 1 Pages 75-80
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The effect of platelet-activating factor (PAF) on histamine release from peritoneal mast cells of adult and young male rats was investigated. PAF alone tended to release histamine from the mast cells of adult and young rats, although very slightly. On the other hand, PAF significantly inhibited the histamine release induced by the Ca2+ ionophore A231 87 in mast cells obtained from rats of either age group, but not that by compound 48/80. Such inhibition was not seen with lyso-PAF. CV-3988, a PAF antagonist, antagonized the inhibitory effect of PAF on the A231 87-induced histamine release in mast cells from adult and young rats. These results suggest that PAF does not have a strong histamine-liberating action on mast cells, and that PAF inhibits the calcium influx into mast cells through the activation of PAF receptors.
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  • Sadao NAKANISHI, Hiroyasu OKUNO
    1990 Volume 53 Issue 1 Pages 81-96
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The effects of three new quinolones (enoxacin (ENX), norfloxacin (NFLX) and ofloxacin (OFLX)) on acetaminophen-induced liver injury in rats were examined and compared with their effects on the elimination half-life (T1/2) of theophylline (in vivo) and on the 7-ethoxycoumarin (7-EC) O-deethylase activity in liver microsomes (in vitro). ENX, NFLX and OFLX (75 or 300 mg/kg) were administered orally to rats 1 hr before, simultaneously with, and 1 hr after the acetaminophen injection (800 mg/kg). Biochemical liver function tests, drug metabolizing activity in liver microsomes, the total glutathione content of the liver and histological changes were examined 5 hr after the acetaminophen injection. ENX markedly reduced acetaminophen-induced liver injury and NFLX slightly but significantly did so, but no protective effect was observed with OFLX treatment. ENX markedly and NFLX slightly prolonged the T1/2 of theophylline, but OFLX did not affect it. In addition, ENX markedly and NFLX slightly inhibited the 7-EC O-deethylase activity in liver microsomes, but OFLX again had no effect. These findings indicated that ENX markedly inhibited the activity of cytochrome P-450 in liver microsomes and NFLX did so slightly, while OFLX had no such effect. Slight variations in the structures of these quinolones might explain the differences in their effects on cytochrome P-450 activity.
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  • Atsushi SUGIYAMA, Shigeru MOTOMURA, Kohji TAMURA, Keitaro HASHIMOTO
    1990 Volume 53 Issue 1 Pages 97-110
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    To assess the cardiovascular profiles of pirmenol, a new antiarrhythmic drug, and to compare them with those of disopyramide, isolated canine sinoatrial node, papillary muscle and atrioventricular node preparations cross-circulated with a donor dog were used. Pirmenol injected intraarterially into the isolated preparations showed negative chronotropic and inotropic effects, which were comparable to those of disopyramide; and it also showed coronary vasodilator and negative dromotropic effects on atrio-His as well as His-ventricular conduction, which were significantly more potent than those of disopyramide. Similarly, pirmenol administered intravenously into the donor dog showed more potent negative dromotropic effects on the PQ interval and QRS width than disopyramide, while in the isolated preparations cross-circulated by the donor dog, pirmenol and disopyramide showed equipotent cardiodepressant effects. In the same preparation, pirmenol decreased coronary blood flow following a transient increase, while disopyramide only decreased coronary blood flow. Since the antiarrhythmic action of class I drugs is considered to result from inhibition of the fast inward current, which generates and propagates action potentials and also induces ventricular automaticity, our results suggest that pirmenol possesses an electrophysiologic effect typical to an efficacious class I agent such as disopyramide.
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  • Ryoji KOJIMA, Mikio ITO, Yoshio SUZUKI
    1990 Volume 53 Issue 1 Pages 111-120
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The mechanism by which latamoxef (LMOX) reduces intrarenal tobramycin (TOB) levels was studied. When TOB (90 mg/kg/day, s.c.) and LMOX (500 or 2000 mg/kg/day, s.c.) were given simultaneously at separate sites to rats, 20 to 30% reductions in intrarenal TOB concentration were found on the 1st and 3rd days, as compared with the results from using TOB alone. The treatment with the reaction mixture of TOB and LMOX, which was preincubated for 3 hr at 37°C to form the complex of TOB and LMOX, resulted in a greater suppression of TOB level in the kidney than administration of TOB and LMOX concomitantly at separate sites. When LMOX was given to rats 0.5 or 1.5 hr before s.c. injection of TOB, there were significant reductions in intrarenal TOB concentration. However, treatment with LMOX 5 hr before, as well as 1.5 or 5 hr after TOB injection, was ineffective in reducing the accumulation of TOB in the kidney. In the rats given both drugs simultaneously, the urinary excretion pattern of TOB almost overlapped with that of LMOX. Additionally, we detected a complex of TOB and LMOX in the urine of rats given both drugs simultaneously. These results suggest that the suppressive action of LMOX on intrarenal TOB level is due to the interaction of TOB and LMOX.
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  • Ming-Yu ZHANG, Tsuneichi HASHIMOTO, Kinya KURIYAMA
    1990 Volume 53 Issue 1 Pages 121-124
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The effect of cold-immobilized stress on the γ-aminobutylic acid (GABA)/ benzodiazepine (BZP) receptor complex in the rat striatum was examined. The stressful manipulation induced a significant decrease in the amount of [3H]muscimol binding sites in the striatal particulate fraction. On the other hand, [3H]flunitrazepam (FLN) binding and the enhancing effect of FLN or secobarbital on the [3H]muscimol binding to the striatal particulate fraction were not influenced by the stress treatment. These results suggest that cold-immobilized stress may selectively change GABAA receptor binding without altering BZP receptor binding as well as the functional coupling between GABAA and BZP receptors.
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  • Chikako NUKI, Hiromu KAWASAKI, Koichiro TAKASAKI
    1990 Volume 53 Issue 1 Pages 125-128
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    The role of neuropeptide Y (NPY) in the neurotransmission of calcitonin gene-related peptide (CGRP)-containing vasodilator nerves was investigated in perfused mesenteric vascular beds of the rat with active tone. NPY (5 and 10 nM) significantly inhibited the neurogenic vasodilation induced by perivascular nerve stimulation (1-8 Hz). However, NPY had no effect on vasodilation in response to bolus infusion of rat CGRP (10 and 100 pmol). These results suggest that NPY modulates the release of CGRP from CGRP-containing nerves in mesenteric resistance vessels.
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  • Yoshihisa NASA, Kazuo ICHIHARA, Yasushi ABIKO
    1990 Volume 53 Issue 1 Pages 129-133
    Published: 1990
    Released on J-STAGE: July 11, 2006
    JOURNAL FREE ACCESS
    In isolated perfused rat hearts, the tissue levels of non-esterified fatty acids (NEFA) decreased during normoxic perfusion for 60 min in the working heart but not in the Langendorff heart. The levels of both saturated and unsaturated NEFA increased during ischemia for 20 min in the working heart but not in the Langendorff heart, although unsaturated NEFA increased in the Langendorff heart when the ischemic period was 40 min. Arachidonic and linoleic acids were the NEFA that accumulated most prominently.
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