The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 86, Issue 1
Displaying 1-19 of 19 articles from this issue
Reviews
  • Norbert König, Sylvie Poluch, Jeanne Estabel, Micheline Durand, M ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 1-17
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    For a long time, alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate (AMPA) receptors permeable to calcium have been considered to be either non-existent or as “atypical”. There is now ample evidence that these receptors exist in numerous regions of the nervous system and in many neuronal as well as non-neuronal cell populations. This evidence has been accumulated by several methods, including electrophysiological recording, calcium imaging and cobalt-loading. Functional AMPA receptors permeable to calcium are already expressed at very early stages of embryonic development, well before the onset of synaptogenesis. They are probably involved in the paracrine signaling necessary for construction of the nervous system before becoming involved in synaptic transmission. In immature cells, cyclothiazide strongly increases the steady-state level of responses not only to AMPA, but also to kainate. Ingestion, during pregnancy, of food or drug substances that can cross the placental barrier and act upon the embryonic receptors may constitute a risk for normal development. In the adult nervous system, synaptic as well as non-synaptic (paracrine) AMPA receptors permeable to calcium are probably widely expressed in both glial and neuronal cells. They may also participate in controlling some aspects related to adult neurogenesis, in particular the migration of newly formed neurons.
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  • Kazuho Abe
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 18-22
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Why are emotionally arousing experiences well-remembered? Since the amygdala and hippocampus play pivotal roles in emotion and memory, respectively, the interaction between these brain regions may underlie the formation of enhanced memory for emotionally arousing events. Behavioral experiments using animals have demonstrated that lesions of the amygdaloid nuclei or infusions of drugs into the amygdaloid nuclei impair or enhance hippocampal-dependent learning. In addition, we have obtained direct evidence that neural inputs from the amygdala modulate synaptic plasticity in the hippocampus, through electrophysiological experiments using anesthetized rats. Electrical stimulation of the basolateral amygdala evoked synaptic potentials in the dentate gyrus of the hippocampus, indicating that there is a neural connection from the amygdala to the hippocampus. Lesion of the basolateral or basomedial, but not central, amygdala resulted in attenuation of long-term potentiation (LTP) at the perforant path-dentate gyrus granule cell synapses. High-frequency stimulation of the basolateral or basomedial amygdala alone did not induce LTP in the dentate gyrus, but facilitated the induction of LTP when applied at the same time as tetanic stimulation of the perforant path. The activity-dependent facilitation of hippocampal LTP by the basomedial and basolateral amygdala may be a synaptic mechanism underlying memory enhancement associated with emotions.
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Full Papers
  • Nobuo Homma, Gozoh Tsujimoto, Keitaro Hashimoto
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 23-31
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    The effects of bidisomide, an antiarrhythmic agent, on sodium current (INa) in isolated rat ventricular myocytes were investigated using a whole cell voltage clamp method. Bidisomide blocked INa with a Ki of 214 μM at a holding potential of −140 mV. The blockade of INa was enhanced at a less negative holding potential of −100 mV with a Ki of 21 μM. Bidisomide shifted the steady state inactivation curve to a negative potential direction by 20 mV without a significant change in the slope factor. Bidisomide slowed the time course of recovery of INa at a holding potential of −140 mV with a slow recovery phase. The time constant of recovery phase for bidisomide, disopyramide and mexiletine were 2703, 1858 and 757 ms, respectively. The development of the block of INa consisted of two phases in the presence of bidisomide. The fast and slow time constants were 11 and 648 ms. Bidisomide produced a use-dependent block of INa when the depolarizing pulse was repeated at 1 - 3 Hz. Our results indicate that bidisomide binds to rat cardiac sodium channels and that the dissociation kinetics of bidisomide from the inactivated sodium channel is slower than that of disopyramide.
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  • Kazuko Satoh, Kazunori Hashimoto, Terumasa Hayakawa, Atsushi Ishige, M ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 32-37
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    To clarify the contractile mechanism of Dai-kenchu-to, the effects of hydroxy β-sanshool (an ingredient of Zanthoxylum fruit), Zanthoxylum fruit (a constituent herb of Dai-kenchu-to) and Dai-kenchu-to were studied in mucosa-free longitudinal muscle of guinea pig ileum. Hydroxy β-sanshool at 107 - 105 g/ml induced dose-related contractions accompanied by autonomous contraction and produced an initial contraction at a concentration of 104 g/ml or more. The contraction induced by hydroxy β-sanshool (105 g/ml) was significantly inhibited by tetrodotoxin or the capsaicin-receptor antagonist capsazepine. Although atropine or the substance P antagonist spantide tended to inhibit the contraction, a combination of atropine and spantide almost abolished the contraction by hydroxy β-sanshool. The P2-purinoceptor antagonist pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid did not affect hydroxy β-sanshool-induced contraction in the presence or absence of spantide. The tonic contractions by Zanthoxylum fruit (2 × 104 g/ml) and Dai-kenchu-to (103 g/ml) were significantly inhibited or tended to be inhibited by atropine, spantide, tetrodotoxin or capsazepine and were remarkably suppressed by the combination of atropine and spantide. These results suggested that acetylcholine release from intrinsic cholinergic nerves and tachykinins from sensory neurons are involved in the contractions induced by hydroxy β-sanshool and that tachykinins may be involved in the atropine-resistant contraction by Dai-kenchu-to.
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  • Zullies Ikawati, Masato Nose, Kazutaka Maeyama
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 38-46
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    In rat trachea, two types of mast cells have been identified, connective tissue mast cells (CTMCs) and mucosal mast cells (MMCs). We previously reported that CTMCs play an important role in tracheal contraction in vitro via 5-hydroxytryptamine (5-HT) release in a rat model. In this study, we investigated whether MMCs also play a role in tracheal contraction by employing mast cell-deficient (Ws/Ws) rats and their congenic (+/+) rats. Rats were actively sensitized with ovalbumin and challenged with it 2 weeks later. To exclude the influence of CTMCs, rats were pretreated for 7 days with compound 48/80 injected i.p. in increasing doses. Histological study confirmed that degranulation occurred in CTMCs, but MMCs still remained. Histamine levels in trachea decreased to 9.31% of control levels. Ovalbumin-specific IgE production showed a time-dependent increase in both Ws/Ws and +/+ rats after sensitization with no significantly different values between the two groups. Ovalbumin challenge caused contraction of the trachea in sensitized control (+/+) rats, but not in sensitized Ws/Ws and compound 48/80-pretreated +/+ rats. Ketanserin inhibited the contraction, but leukotriene antagonist ONO-1078 did not, indicating that the contraction was due to 5-HT, whereas leukotriene, a mediator specific derived from MMCs, has no significant effect. The results suggest that MMCs has minimal, if any, contribution to tracheal contraction and might have another function. Furthermore, Ws/Ws and the congenic rats provide a good model for studying the role of mast cells in the immunologic response in airways.
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  • Junzo Kamei, Masahiro Ohsawa, Minoru Tsuji, Hiroshi Takeda, Teruhiko M ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 47-54
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    The effect of diabetes on the emotional behavior of mice was examined using an automatic hole-board apparatus. Changes in the emotional state of mice were evaluated in terms of changes in exploratory activity; i.e., total locomotor activity, numbers and duration of rearing and head-dipping, and latency to the first head-dipping. The number and duration of head-dipping in diabetic mice were less than those in non-diabetic mice. Diazepam (0.1 - 0.56 mg/kg, i.p.) dose-dependently increased the number and duration of head-dipping at doses that did not produce sedation in both diabetic and non-diabetic mice. In contrast, methyl-β-carboline-3-carboxylate (1 and 2 mg/kg, i.p.) decreased the number and duration of head-dipping in non-diabetic mice, but not in diabetic mice. The number and duration of head-dipping in diabetic mice were increased by treatment with flumazenil (0.1 and 0.3 mg/kg, i.v.). These doses of flumazenil did not affect the number or duration of head-dipping in non-diabetic mice. The present data indicate that diabetic mice exhibited anxiety in the hole-board test and that a benzodiazepine receptor antagonist affected the attenuated number and duration of head-dipping in diabetic mice. The heightened anxiety in diabetic mice may be due to the dysfunction of the benzodiazepine receptor and/or of central inhibitory systems.
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  • Toshiaki Takizawa, Jiro Matsumoto, Tsutomu Tohma, Toru Kanke, Yasushi ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 55-64
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    The pharmacological properties of 7-{3-[4-(2-quinolinylmethyl)-1-piperazinyl]-propoxy}-2,3-dihydro-4H-1,4-benzothiazin-3-one (VUF-K-8788) were investigated in vitro and in vivo. VUF-K-8788 inhibited [3H]-mepyramine from binding to the cell membrane of lung parenchyma (Ki value: 5.0 nM) and the histamine-induced contraction of isolated guinea pig ileum (pA2: 9.71) without affecting ileal contractions induced by acetylcholine, serotonin, KCl and BaCl2. The increase of vascular permeabilities induced by histamine and passive cutaneous anaphylaxis (PCA) in guinea pigs were inhibited by VUF-K-8788 in a dose-dependent fashion (ED50: 0.24 and 0.26 mg/kg, p.o., respectively). Moreover, the anti-histaminic effect of VUF-K-8788 was also observed in rats. In experiments on the effects on the central nervous system, VUF-K-8788 at 1 mg/kg, p.o. hardly antagonized the H1 receptor at all in the cerebral cortex of guinea pigs. VUF-K-8788 inhibited the PCA-induced scratching behavior completely without affecting thiopental-induced sleep in mice. These results suggested that VUF-K-8788 would be useful in the treatment of allergic disorders such as atopic dermatitis and eczema.
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  • Chiharu Aoki Sogawa, Norio Sogawa, Toshio Yamamoto, Nariaki Oda, Tetsu ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 65-72
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    We investigated the induction of metallothionein (MT) by cadmium (Cd) in the dental pulp of rat incisors. Time-course studies of MT mRNA expression after single Cd injection were observed by Northern-blot analysis. The isoform-specific expressions of MT mRNAs (MT-I, MT-II and MT-III) were observed using the reverse transcriptase-polymerase chain reaction (RT-PCR) method. Both MT-I and MT-II mRNA levels increased within 3 h, peaked at 3 h and then decreased. These findings demonstrated that MT-I and MT-II mRNA were rapidly induced by Cd in dental pulp. MT-III mRNA was constitutively expressed in rat dental pulp, but the expression level did not change by Cd treatment. The localization of MT protein in Cd-treated rat dental pulp was determined by immunohistochemical staining using anti-MT antibody against MT-I and MT-II. MT protein was localized in the specific cell type of odontoblasts (secretory odontoblasts and resting odontoblasts). In conclusion, it is likely that stained MT in the immunohistochemical study should be MT-I and/or MT-II. Furthermore, MT-I and/or MT-II in Cd-treated rat dental pulp was localized in odontoblasts, in which accumulation of Cd were reported. The cell-specific synthesis of MT may be associated with its metal storage and detoxification role in dental tissues.
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  • Akira Furuichi, Noriaki Makimoto, Masayuki Ogishima, Kanichirou Nakao, ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 73-78
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Intestinal motor activity associated with acetylcholine (ACh) release was assessed in the small intestine of anesthetized dogs by simultaneous measurement of motor activity and local ACh concentrations within the intestinal wall with in vivo microdialysis. Basal concentration of ACh measured in the dialysate was 1.12 ± 0.08 pmol/15 min (n = 10), a value that remained constant until 3 h after perfusion. Intraarterial infusion of tetrodotoxin reduced dialysate ACh concentration, while the motor activity accelerated at the early phase after infusion of tetrodotoxin and then decreased, thereby suggesting that the motor activity is regulated by not only excitatory cholinergic neurons, but also inhibitory neurons. Intraarterial infusion of atropine increased dialysate ACh concentration but reduced motor activity, thereby indicating that the cholinergic neurons are tonically active and the muscarinic autoreceptors operate to inhibit the ACh release. Intraarterial infusion of norepinephrine reduced, but yohimbine increased both motor activity and dialysate ACh concentration, thereby indicating that the adrenergic neurons regulate the motor activity due to control of cholinergic neuronal activity. This in vivo microdialysis method demonstrated in the whole body of animals that the activity of cholinergic neurons was physiologically regulated by itself and adrenergic neurons.
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  • Tomoko Tokioka-Akagi, Akira Fujimori, Masayuki Shibasaki, Osamu Inagak ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 79-85
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    We evaluated the effects of chronic oral administration of an angiotensin II type 1 (AT1)-receptor antagonist YM358 and an angiotensin converting enzyme inhibitor enalapril on hemodynamics and cardiac hypertrophy in rats with volume overload-induced heart failure. We assessed changes of cardiac hemodynamics and cardiac hypertrophy at 2 and 4 weeks after administration of YM358 (3, 30 mg/kg per day) or enalapril (30 mg/kg per day) in abdominal aortocaval shunt rats. YM358 (30 mg/kg) attenuated increases of left ventricle (LV)/body weight (BW), left atrium (LA)/BW, right ventricle (RV)/BW and heart/BW ratios, but did not affect cardiac hemodynamics in shunt rats. Enalapril also reduced the increased LV/BW and heart/BW ratios together with significant reductions of systolic blood pressure, left ventricular systolic pressure and the first derivative of left ventricular pressure. These data suggest that the effects on attenuation of the development of cardiac hypertrophy are not different for YM358 and enalapril, although the effects on cardiac hemodynamics are different for the same dosages. The attenuating action of YM358 on cardiac hypertrophy was independent of the action on hemodynamics and indicated the direct action of the AT1 receptor on the heart.
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  • Takashi Fujita, Nobuo Izumo, Ryo Fukuyama, Toru Meguro, Chigusa Yasuto ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 86-96
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Two types of bisphosphonates (BPs), incadronate (INC) and etidronate (ETI) accelerated phosphate (Pi)-primed mineralization of MC4 cells in a subnanomolar dose range. Intracellular signaling pathways involved were examined. 1) The effect of INC but not ETI was partially suppressed by two mevalonate (MVA) pathway metabolites, farnesylpyrophosphate (FPP) and geranylgeranylpyrophosphate (GGPP). 2) The BP-like accelerating effect was produced by statins and also by Toxin B, a Rho GTPases-specific inhibitor. 3) INC induced Cbfa1-nuclear localization within hours; and in an in vivo experiment using ovariectomized mice, its 3 weeks dosing exhibited the same effect in tibial extracts. 4) BPs promoted luciferase expression in murine p1.3-osteocalcin gene 2-luc and p6-osteoblast specific element 2-luc transfected cells, just as MVA, FPP and GGPP did independently and additively to INC. 5) BPs activated extracellular signal-regulated kinase (ERK1/2) in a Ras-independent manner within 5 min, and Pi was found to sensitize MC4 cells to BPs. MVA and its metabolites also activated ERKs but in a Ras-dependent manner and additively to INC. Ras dependency was determined using N17Ras-transfected cells. A MEK (MAP kinase-ERK kinase)-specific inhibitor PD98059 alone partly and with FPP completely blocked INC-induced mineralization. The results suggest that BPs act on Pi-sensitized MC4 cells to accelerate mineralization via nonRas-MEK-ERK1/2-Cbfa1 transactivation pathway and INC additionally acts by inhibiting the MVA pathway.
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  • Eiji Ohtsuka, Sanae Kawai, Tomohiro Ichikawa, Hiroshi Nojima, Kanji Ki ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 97-105
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    We investigated itch-associated responses (scratching) to mosquito bites and the role of histamine and mast cells in mosquito-induced itching in mice. Although the first bites of mosquito Aedes albopictus did not increase scratching, repeated bites increased scratching. The response was not diminished even after an interval of 2 months. Similarly, repeated intradermal (i.d.) injections of salivary gland extract (SGE) from Aedes albopictus increased scratching after SGE injection itself and mosquito bites. The scratching peaked within 10 min and almost subsided by 60 min. The opioid antagonist naloxone (1 mg/kg, s.c.) inhibited scratching following SGE injection. Although the non-sedative H1-histamine-receptor antagonist terfenadine (30 mg/kg, p.o.) significantly suppressed scratching induced by histamine (100 nmol/site, i.d.) in either naive or mosquito-sensitized mice, it did not affect mosquito-induced scratching in mosquito-sensitized mice. Repeated injections of SGE increased scratching in mast cell-deficient (WBB6F1-W/Wv) mice as well as in normal (WBB6F1-+/ +) littermates. Repeated exposure to mosquito bites roughly doubled serum concentrations of total IgE and IgG1, but not IgG2a. Repeated injections of SGE markedly increased plasma extravasation induced by mosquito bites and such an increase was almost completely suppressed by terfenadine (30 mg/kg, p.o.). The results show the presence of histamine-mediated and histamine-independent mechanisms in cutaneous itching and suggest that histamine probably released from mast cells does not play an important role in itching in immediate allergic reaction. Our murine model of mosquito itching may be useful for studying the mechanisms of immediate allergic itching.
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  • Yoshiaki Ohi, Nobuhiko Takai, Katsuhiko Muraki, Minoru Watanabe, Yuji ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 106-113
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Simultaneous recording of Ca2+-images in one confocal plane from vascular smooth muscle cells (SMCs) and endothelial cells (ECs) of an intact rat femoral artery segment was performed using indo-1 and a confocal microscope. During application of 10 μM acetylcholine (ACh), elevation and oscillation of intracellular Ca2+ concentration ([Ca2+]i) were observed in ECs but not in SMCs. Sequential conduction of Ca2+ oscillation from an EC to the neighboring ECs in one longitudinal direction was often observed in the presence of ACh. On the other hand, the activation of voltage-dependent Ca2+ channels by external 30 mM K+ resulted in the elevation of [Ca2+]i only in SMCs. When 10 μM ACh was added in the presence of 30 mM K+, it was observed in one confocal plane that [Ca2+]i in ECs and SMCs was almost simultaneously increased and decreased, respectively. The simultaneous recording method in this intact preparation will provide a line of valuable information about the interactions between SMCs and ECs, based on spatio-temporal analyses of absolute values of [Ca2+]i in individual cells.
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  • Shigeki Miyamoto, Bing-Mei Zhu, Nu Nu Aye, Keitaro Hashimoto
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 114-119
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    We investigated the effects of prolonged repolarization induced by slowed inactivation of Na+ channel on adrenaline-induced arrhythmias in halothane anesthetized, closed-chest dogs. We used sea anemone toxins (ATX-II and Anthopleurin-A) to prolong ventricular repolarization and examined their effects on adrenaline arrhythmias. Sea anemone toxins prolonged the QTc- and JTc-intervals (P<0.01), but did not affect the PQ interval, QRS duration, heart rate and mean blood pressure. Although sea anemone toxins did not induce any arrhythmias by themselves, under the treatment with these toxins, arrhythmias were induced by non-arrhythmia-inducing doses of adrenaline in four dogs out of seven and the control arrhythmias induced by adrenaline were aggravated. These results indicate that, similar to the inhibition of K+ channels by class III drugs, which we have already reported, slowing Na+ channel inactivation with QTc prolongation also aggravates adrenaline-induced arrhythmias.
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Short Communications
  • Yukimasa Azuma, Katsuhiro Date, Katsutoshi Ohno, Shoichiro Matsushiro, ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 120-123
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    The cholesterol-lowering and anti-atherosclerotic effects of NTE-122 (trans-1,4-bis[[1-cyclohexyl-3-(4-dimethylaminophenyl)ureido]methyl]cyclohexane), an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor, were evaluated in 1% cholesterol diet-fed rabbits. NTE-122 (1, 3 and 10 mg/kg per day) lowered the total cholesterol levels in both plasma and liver dose-dependently (by 99% and 94% at 10 mg/kg per day, respectively). In the aortic wall of the rabbits given NTE-122, the atherosclerotic lesion area in both aortic arch and thoracic aorta were dose-dependently reduced (by 100% at 10 mg/kg per day), and the total cholesterol content in aortic arch was also lowered significantly at more than 3 mg/kg per day. These results suggest that NTE-122 is capable of exhibiting anti-atherosclerotic effects.
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  • Shinji Takai, Denan Jin, Masato Sakaguchi, Kazuyoshi Kirimura, Mizuo M ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 124-126
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    We investigated the effects of a novel chymase inhibitor, BCEAB (4-[1-{[bis-(4-methyl-phenyl)- methyl]-carbamoyl}-3-(2-ethoxy-benzyl)-4-oxo-azetidine-2-yloxy]-benzoic acid). The IC50 value of BCEAB for purified human chymase was 5.4 nM, whereas BCEAB did not inhibit the angiotensin-converting enzyme, elastase and tryptase. In isolated dog arteries, the IC50 value of BCEAB for the angiotensin I-induced contraction in the presence of 1 μM lisinopril was 2.8 μM. In the hamster, the heart chymase activities were significantly suppressed to 42.0% and 26.9% 3 h after oral administration of 100 and 300 mg of BCEAB/kg of body weight, respectively. In conclusion, BCEAB is a useful chymase inhibitor for studying the role of chymase in vivo.
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  • Koji Fujinami, Kazuhiro Kojima, Katsumi Aragane, Jun Kusunoki
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 127-129
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Postprandial hyperlipidemia (PH) is frequently observed in diabetic patients. We performed an oral fat-loading test in Zucker diabetic fatty (ZDF) fa/fa rats, a model for type II diabetes, to determine whether PH was induced in the rats. Post fat-loading changes in serum cholesterol and triglyceride levels were significantly greater in the fa/fa rats than those seen in their lean littermates and an acyl-CoA:cholesterol acyltransferase (ACAT) inhibitor significantly reduced these levels by 24% and 31%, respectively. Therefore, we confirmed that PH appeared in ZDF fa/fa rats by fat loading and ACAT inhibition may be a potential treatment for PH.
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  • Gang Cheng, Takashi Ueda, Fukiko Eda, Syunichi Kinjyo, Hirokazu Nakaji ...
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 130-133
    Published: 2001
    Released on J-STAGE: July 10, 2001
    JOURNAL FREE ACCESS
    Tranilast has long been used clinically to treat allergic diseases such as bronchial asthma. To further clarify the antiinflammatory machanism, we examined the ability of tranilast to counteract the prolongation of eosinophil survival induced by interleukin (IL)-5. Tranilast reduced the IL-5 prolonged survival of eosinophils at the concentration range of 30 μg/ml to 100 μg/ml. The DNA extracted from eosinophils cultured with tranilast showed signs of fragmentation that was comparable with apoptosis. Electron-microscopic analysis of activated eosinophils cultured with 100 μg/ml of tranilast also revealed morphologic features of apoptosis. These data suggest that tranilast may act in vivo on activated eosinophils to reduce inflammation in allergic diseases.
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  • Hiroki Okada, Motoko Honda, Hideki Ono
    Subject area: Infomation Science
    2001 Volume 86 Issue 1 Pages 134-136
    Published: 2001
    Released on J-STAGE: July 10, 2001
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    Mice were used to record the spinal reflex potentials and to examine the effects of some drugs upon them. In anesthetized mice, laminectomy was performed in the lumbo-sacral region, and monosynaptic reflex potential (MSR) and polysynaptic reflex potential were recorded from the L5 ventral root after stimulation of the L5 dorsal root. Thyrotropin-releasing hormone (TRH) and 1-(4-iodo-2,5-dimethoxyphenyl)-2-aminopropane hydrochloride (DOI) produced transient and long-lasting increases in the MSR amplitude, respectively. Tolperisone hydrochloride and baclofen produced transient and long-lasting MSR depressions, respectively. These results show that mice can be used to record spinal reflex potentials, and that it may be possible to study the spinal cord function of mutant and knockout mice using this method.
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