The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 69 , Issue 4
Showing 1-20 articles out of 20 articles from the selected issue
  • Yoko Omura
    1995 Volume 69 Issue 4 Pages 293-302
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    For a further understanding of the inhibitory effect of NaCI on hog kidney mitochondrial monoamine oxidase (MAO), the activity for benzylamine as substrate was assayed spectrophotometrically in the absence and presence of NaCI for mitochondrial outer membrane preparations as well as whole mitochondria. The effect of CaC12 was also examined for comparison. The inhibition by NaCI but not CaC12 was strongly pH dependent. The pH dependence of the inhibitory effect of NaCI in phosphate buffer was parallel to the pH dependence of the MAO activity itself. The point at which the slope of the Arrhenius plot in the absence of NaCl decreases with increasing temperature was to be 32.3°C at pH 7.0 and 30.4°C at pH 7.5 in phosphate buffer, while the Arrhenius plot in the presence of NaCI exhibited discontinuities without change in the slope in small temperature ranges, 39.2°C-40.0°C and 33.0°C-34.2°C. It was estimated that the inhibitory effect of NaCl was due to a pH and temperature sensitive cooperative state change involving MAO protein and boundary lipids, while the effect of CaC12 could be induced by specific Ca2+ binding to acidic phospholipids.
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  • Noritsugu Tohse, Morio Kanno
    1995 Volume 69 Issue 4 Pages 303-309
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The effects of dofetilide (UK 68798) on membrane currents were examined in isolated sinoatrial node cells of rabbits by using patch clamping. At a concentration of 1 pM, dofetilide decreased the delayed rectifier K+ current (IK) (50.2±10.2%, mean±S.E.). The Ca2+ current was slightly decreased during the application of dofetilide. However, the decrease in the current may be attributed to the “run down” phenomenon. The drug did not affect the hyperpolarization-activated inward current. Therefore, dofetilide exhibited class III antiarrhythmic activity in rabbit sinoatrial node cells. Similarly, E-4031 (1-[2-(6-methyl-2-pyridyl)ethyl]-4-(4-methylsulfonylaminobenzoyl)pireridine) (1 μM), a standard class III agent, also showed specific inhibition of IK. Furthermore, dofetilide depolarized the maximum diastolic potentials, reduced the slope of the pacemaker potential and then abolished spontaneously firing action potentials in the nodal cells. The results demonstrate that dofetilide may produce negative chronotropic effects as a result of its class III activity.
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  • Peng-Jiang Chu, Akira Shirahata, Keijiro Samejima, Hiroshi Saito, Kazu ...
    1995 Volume 69 Issue 4 Pages 311-315
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We previously found that spermine potently promotes the neuronal survival and regeneration of primary cultured brain neurons. N-(3-Aminopropyl)cyclohexylamine (APCHA) was originally developed as a spermine synthase inhibitor. To test if endogenous spermine biosynthesis contributes to neuronal survival and morphogenesis, we examined the effects of APCHA in primary cultured rat hippocampal and cerebellar neurons. APCHA at concentrations up to 10-6 M did not affect the neuronal survival, but significantly blocked the survival-promoting effect of spermine (10-8 M). APCHA also blocked the spermine-induced promotion of neurite regeneration following axotomy. Unlike APCHA, another cyclohexylamine derivative trans-4-methylcyclohexylamine did not affect the neurotrophic effect of spermine. These results suggest that in primary cultured brain neurons, APCHA works as a spermine antagonist rather than as a spermine synthesis inhibitor.
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  • Susumu Okabe, Yusuke Takinami, Kazumi Iwata, Tsukimi Yanagawa
    1995 Volume 69 Issue 4 Pages 317-323
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We examined the effect of leminoprazole (an acid pump inhibitor) on reflux esophagitis induced in rats. Intragastrically administered leminoprazole significantly and dose-dependently protected the esophageal mucosa against the reflux of gastric contents, without affecting gastric acid secretion. However, it had no effect on the esophagitis when administered intraduodenally, despite its significant inhibition (about 40%) of gastric acid secretion. Omeprazole significantly prevented the development of esophagitis, most probably through potent inhibition of gastric acid secretion. Indomethacin significantly reduced the synthesis of prostaglandin E2 in the esophagus. Since indomethacin pretreatment had no effect on the esophageal protection by leminoprazole, omeprazole or sucralfate, the involvement of endogenous prostaglandins can be ruled out as a possible underlying mechanism. Intragastrically, but not intraduodenally, administered sucralfate significantly prevented the esophagitis even at a dose not affecting gastric acid secretion. These results strongly suggest that both leminoprazole and sucralfate protect the esophageal
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  • Renbin Huang, Hiroyasu Okuno, Masashi Takasu, Yasuko Shiozaki, Kyoichi ...
    1995 Volume 69 Issue 4 Pages 325-334
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    Rifampicin conferred significant protection against carbon tetrachloride (CCl4)-induced liver injury. Serum alanine transaminase (ALT) and aspartate transaminase (AST) activities were not markedly altered and only hepatocellular fatty degeneration was found in mice pretreated with rifampicin (200 mg/kg), whereas severe centrilobular necrosis was observed and serum ALT and AST activities were as high as 281 and 271 I.U./1, respectively, in the control group following administration of CCl4 (400μl/kg). The contents and activities of microsomal drug-metabolizing enzymes in rifampicin-pretreated animals were also much higher than those of the controls. CCl4-mediated malondialdehyde (MDA) formation was increased in rifampicin-treated liver microsomes, demonstrating that rifampicin was capable of increasing the NADPH-dependent metabolism of CCl4 catalyzed by P-450 2E1 to produce free radicals. However, MDA formation was obviously depressed by rifampicin at varying concentrations from 2 to 32 x 10-6 M in an in vitro cytochrome P-450 (P-450) enzyme system. On the other hand, NADPH oxidation in the metabolism of CCl4 and aniline hydroxylation were not suppressed in the presence of rifampicin in this systems, suggesting that rifampicin did not influence the biotransformation of CCl4 by P-450 2E1 in vitro. Therefore, the protective effect of rifampicin against CCl4 hepatotoxicity appeared to result from the direct inhibition of lipid peroxidation generated by CCl4-derived free radicals.
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  • Yoshihiro Futamura
    1995 Volume 69 Issue 4 Pages 335-341
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    I studied the effect of amiodarone, a cationic amphiphilic drug, on the cytokine release and protein kinase C (PKC) activity of mouse alveolar macrophages. In addition, I examined the relationship between amiodarone and eicosapentaenoic acid (EPA) with respect to the cytokine release. The decrease in cell number caused by amiodarone was depressed by pretreatment of the macrophages with EPA for 2 days and co-treatment for 1 day. These changes reflected the potency of EPA to protect against the cell injury elicited by amiodarone. As regards to the cytokine release, amiodarone caused an increase in interleukin (IL)-1α, IL-1β and tumor necrosis factor (TNF)α release from macrophages. As EPA suppressed this increase in cytokine levels, I considered that the protective effect of EPA may be extended to the acute release of cytokines. PKC activity was increased by amiodarone, and this increase was depressed by EPA. These changes were well-related to the results on cytokine levels in this study, indicating that amiodarone firstly activated PKC, leading to the stimulation of release of cytokines and that pretreatment with EPA prevented these effects. I conclude that mouse alveolar macrophages treated with amiodarone show activated release of cytokines and that EPA depresses these increases, thereby demonstrating EPA’s anti-inflammatory effect and protective action against injury of alveolar macrophages.
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  • Yoji Sato, Satomi Adachi-Akahane, Pablo Prados, Kazuhiro Imai, Taku Na ...
    1995 Volume 69 Issue 4 Pages 343-350
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We studied the effects of prolonged infusion of a selective β1-adrenoceptor (β1AR) full agonist, T-0509 [(-)-(R)-1-(3, 4-dihydroxyphenyl)-2-[(3, 4-dimethoxyphenethyl)amino]ethanol hydrochloride], with regard to its inotropic effect in vivo and cardiac βAR density. The results were compared with those for isoproterenol. Continuous infusion of isoproterenol at doses of 2.5-40 μg/kg/hr, s.c. for 6 days shifted the dose-response curves of isoproterenol (i.v.) for LVdP/dtmax to the right and increased the ED50 values up to fourfold. Isoproterenol infusion at 40 μg/kg/hr reduced the density of both β1- and β2ARs by 36010 and 43070 respectively, in left ventricular membranes. Following 6-day infusion of T-0509 at doses sufficient to induce a positive inotropic effect (5-40 μg/kg/hr), the ED50 value of T-0509 (i.v.) for LVdP/dtmax was also increased up to fourfold. In contrast to isoproterenol, infusion of T-0509 caused selective down-regulation of β1ARs by 30% without changing the number of β2ARs. These results indicate that long-term application of a selective β1AR full agonist causes desensitization to its inotropy in vivo, with subtype-selective down-regulation of β1ARs in cardiac ventricles.
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  • Mayumi Yamano, Hiroyuki Ito, Takeshi Kamato, Keiji Miyata
    1995 Volume 69 Issue 4 Pages 351-356
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We evaluated the inhibitory effects of YM060 {(R)-5-[(1-methyl-1H-indol-3-yl)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole monohydrochloride} and YM114 (KAE-393) {(R)-5-[(1-indolinyl)carbonyl]-4, 5, 6, 7-tetrahydro-1H-benzimidazole monohydrochloride} on the von Bezold-Jarisch reflex (BJR) induced by 2-methyl-5-HT, a selective serotonin (5-HT)3-receptor agonist; veratridine, which stimulates chemoreceptors and baroreceptors; and electrical stimulation of vagal efferent nerves in anesthetized rats. Results were compared with those of ondansetron and granisetron. 2-Methyl-5-HT (5-160 μg/kg, i.v.) and veratridine (100-200 μg/kg, i.v.) dose-dependently decreased the heart rate (BJR). YM060, YM114, ondansetron and granisetron dose-dependently inhibited 2-methyl-5-HT (40 μg/kg, i.v.)-induced BJR, with ID50 values of 0.012, 0.060, 0.97 and 0.15 μg/kg, i.v., respectively. Their 5-HT3 receptor blocking potencies against 2-methyl-5-HT-induced BJR were largely consistent with those against 5-HT-induced BJR. In contrast, higher doses (100 μg/kg, i.v.) of YM060, YM114, ondansetron and granisetron did not inhibit veratridine (150 μg/kg, i.v.)-induced BJR. Atropine (300 μg/kg, i.v.) abolished bradycardia induced by electrical stimulation of vagal efferent nerves, whereas YM060, YM 114, ondansetron and granisetron had no effect at a dose of 1000 μg/kg, i.v. 5-HT (0.625-5.0 μg) injected into the left ventricle also caused a dose-dependent decrease in heart rate, an effect that was abolished by YM060 (0.1 μg/kg, i.v.), atropine (100 μg/kg, i.v.) and vagotomy. These results suggest that YM060 and YM114 are highly potent and selective 5-HT3-receptor antagonists that do not affect veratridine- or electrical stimulation-induced bradycardia in anesthetized rats. They also suggest that 5-HT-induced BJR in anesthetized rats originates from 5-HT3 receptors located on the endings of vagal afferent nerves in the heart.
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  • Toshio Matsuda, Takashi Yoshikawa, Makoto Suzuki, Shoichi Asano, Prane ...
    1995 Volume 69 Issue 4 Pages 357-366
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The present study characterizes the neurochemical profile of the newly synthesized compound 5-{3-[((2S)-1, 4-benzodioxan-2-ylmethyl)amino]propoxy}-1, 3-benzodioxole HC1 (MKC-242). In in vitro experiments, MKC-242 had high affinity for serotonin1A (5-HT1A) receptors (K1: 0.35 nM) and moderate affinity for α1-adrenoceptors (Ki: 21 nM), whereas it had no appreciable affinity for any other neurotrans-mitter recognition sites studied and 5-HT transporter. MKC-242 (0.3-3.0 mg/kg, s.c.; 1-10 mg/kg, p.o.) caused presynaptic 5-HT1A-receptor-mediated responses (decreases in 5-HT turnover and 5-HT release) and postsynaptic 5-HT1A-receptor-mediated responses (hypothermia, an increase in serum corticosterone level and 5-HT1A behavioral syndrome). The effects of MKC-242 on decarboxylase inhibitor-induced 5-hydroxytryptophan accumulation and rectal temperature were blocked by the 5-HT1A-receptor antagonist N-tert-butyl-3-(4-(2-methoxyphenyl)piperazin-1-yl)-2-phenylpropanamide. The comparative studies on the in vivo responses induced by MKC-242 and the 5-HT1A-receptor full agonist 8-hydroxy-2-(di-n-propyl-amino)tetralin (8-OH-DPAT) showed that MKC-242 and 8-OH-DPAT had similar efficacy at presynaptic 5-HT1A receptors, whereas the former had less efficacy than the latter at postsynaptic 5-HT1A receptors. Furthermore, MKC-242 partially inhibited forskolin-stimulated adenylate cyclase activity in hippocampal membranes. These findings suggest that MKC-242 acts as a full and partial agonist at pre- and postsynaptic 5-HT1A receptors, respectively, in the central nervous system.
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  • Yoshinobu Yamazaki, Kazuhiko Shinagawa, Hiroo Takeda, Mamoru Kobayashi ...
    1995 Volume 69 Issue 4 Pages 367-373
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The effects of KSG-504 ((S)-arginium (R)-4-[-N-(3-methoxypropyl)-N-pentylcarbamoyl]-5-(2-naphthylsulfonyl) pentanoate monohydrate), a new cholecystokinin (CCK)-receptor antagonist, on 125I-CCK-8 binding to rat pancreatic, canine gallbladder and guinea pig cerebrocortical membranes and the pancreatic amylase release from isolated rat acini stimulated by several kinds of secretagogues, including CCK, were investigated. The 125I-CCK-8 saturation experiment showed that pancreatic, gallbladder and cerebrocortical CCK receptors had a single high affinity binding component with dissociation constants (Kd) of 0.18, 0.31 and 0.88 nM, respectively. The maximum numbers of specific binding sites (Bmax) in these membranes were 1012, 52 and 20 fmol/mg protein, respectively. KSG-504 and CCK-8 displaced specific 125I-CCK-8 binding to CCK receptors in all membrane preparations in a competitive manner. The affinity of KSG-504 for pancreatic (Ki=173 nM) and gallbladder (Ki=283 nM) CCK receptors were > 3 orders of magnitude higher than its affinity for cerebrocortical CCK receptors. KSG-504 also inhibited 125I-gastrin-I binding to guinea pig gastric glands, but the IC50 value (18.2 μM) was apparently much higher. CCK-8-stimulated amylase release from isolated pancreatic acini of rats was antagonized by KSG-504 in a concen-tration-dependent manner. KSG-504 did not affect amylase release stimulated by secretagogues such as gastrin-releasing peptide, carbachol, vasoactive intestinal peptide and A23187. These results indicate that KSG-504 acts as a CCK-A-receptor-specific antagonist in the pancreas and gallbladder.
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  • Yoshimichi Okayama, Jun Hiroi, Laurie C.-K. Lau, Martin K. Church
    1995 Volume 69 Issue 4 Pages 375-380
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We have examined the effects of a new anti-allergic drug, quinotolast [sodium 5-(4-oxo-1-phenoxy-4H-quinolizine-3-carboxamido) tetrazolate monohydrate], in inhibiting the release of histamine and the generation of leukotriene (LT) C4 and prostaglandin (PG) D2 from dispersed human lung cells and compared this with those of its active metabolite in the rat, hydroxy quinotolast, and reference drugs, tranilast and sodium cromoglycate (SCG). Quinotolast in the concentration range of 1-100 μg/ml inhibited histamine and LTC4 release in a concentration-dependent manner. The inhibitory effect of quinotolast on histamine release from dispersed lung cells was largely independent of the preincubation period, no tachyphylaxis being observed. Hydroxy quinotolast and tranilast showed a weak inhibition of histamine release only when the drugs were added to the cells simultaneously with anti-IgE challenge. Quinotolast, 100 μg/ml, and SCG, 1 mM, significantly inhibited PGD2 and LTC4 release. Quinotolast inhibited PGD2 release by 100% and LTC4 release by 54%, whereas SCG inhibited PGD2 release by 33% and LTC4 release by 100%. No cross-tachyphylaxis between quinotolast and SCG was observed. The results demonstrated that quinotolast showed a significant inhibition of inflammatory mediators from human dispersed lung cells, suggesting that quinotolast is a good candidate for a clinical anti-allergic drug.
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  • Yosuke Tojyo, Akihiko Tanimura, Yoshito Matsumoto
    1995 Volume 69 Issue 4 Pages 381-389
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The effects of three serine/threonine protein phosphatase inhibitors, calyculin-A, tautomycin and okadaic acid, on the Ca2+ entry across the plasma membrane was studied in Fura-2-loaded rat parotid acinar cells. These protein phosphatase inhibitors did not affect the peak elevation of cytosolic free Ca2+ concentration ([Ca2+]i) just after stimulation with the muscarinic agonist carbachol (CCh), but they suppressed the sustained increase in [Ca2+]i. In the absence of extracellular Ca2+, CCh produced a transient increase in [Ca2+]i due to Ca2+ release from intracellular Ca2+ stores, and this increase in [Ca2+]i was unaffected by the phosphatase inhibitors. When Ca2+ was added to the external medium after the transient [Ca2+]i response, the increase in [Ca2+]i in the cells treated with the phosphatase inhibitors was significantly smaller than that in the control cells, indicating that the Ca2+ entry was reduced. Similar suppression of Ca2+ entry by the phosphatase inhibitors was observed when intracellular Ca2+ stores were previously depleted by the microsomal Ca2+-ATPase inhibitor thapsigargin (TG). In addition, the phosphatase inhibitors reduced the Mn2+ (Ca2+ surrogate) influx following the addition of CCh or TG. The enhancement of Ca2+ entry by the protein kinase inhibitor staurosporine was significantly attenuated by the phosphatase inhibitors. These results suggest that the phosphatase inhibitors suppressed the Ca2+ entry mechanism activated by depletion of intracellular Ca2+ stores in rat parotid acinar cells. The capacitative Ca 2+ entry may be regulated by protein phosphorylation/dephosphorylation.
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  • Mariko Nishiyama, Yoshiharu Takahara, Tomoh Masaki, Nobuyuki Nakajima, ...
    1995 Volume 69 Issue 4 Pages 391-398
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    To study endothelin receptor subtypes that mediate the smooth muscle contraction of human saphenous vein, effects of some endothelin-receptor agonists and antagonists were examined. Endothelin (ET)-1 and sarafotoxin 6b (S6b) elicited potent concentration-dependent contractions with similar pD2 values and similar maximal responses. Selective ETB-receptor agonists, sarafotoxin 6c (S6c) and IRL1620 (Suc-[Glu9, Ala11, 15]-endothelin-1(8-21)), also caused contractions, but their maximal responses were about one third of that of ET-1. ET-3 showed a biphasic concentration-response curve. An ETA-receptor antagonist, BQ-123 (cyclo(-D-Asp-L-Pro-D-Val-L-Leu-D-Trp-)), an ETA/ETB-receptor antagonist, PD142893 (Ac-D-Dip-Leu-Asp-Ile-Ile-Trp), or the combination of these two antagonists hardly affected the contractile effect of ET-1, while each of them markedly antagonized the effects of higher concentrations of ET-3 and S6b. Contractions induced by lower concentrations of ET-3 and S6b were resistant to these antagonists. The concentration-response curves for S6c and IRL1620 were not affected by BQ-123. The effect of IRL1620 was markedly inhibited by PD142893, while S6c-induced contractions were much more resistant to PD142893. These different sensitivities to antagonists suggested heterogeneity of both ETA- and ETB-receptors [ETA1 (sensitive to BQ-123), ETA2 (resistant to BQ-123), ETB1 (sensitive to PD142893) and ETB2 (resistant to PD142893)] in the human saphenous vein, although contractions mediated by ETB-subtypes have smaller maximal responses than those mediated by the ETA-subtypes.
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  • Alain Schotte, Pascal Bonaventure, Paul F.M. Janssen, Josee E. Leysen
    1995 Volume 69 Issue 4 Pages 399-412
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    Risperidone was compared with antipsychotics hitherto used for in vitro receptor binding using animal brain or cloned (human) receptors and in vivo receptor occupancy in rat and guinea pig brain following acute treatment. Both in vitro and in vivo, risperidone, 9-OH-risperidone, SM-9018, clozapine and clocapramine showed higher affinity for 5-HT2A- than for D2-receptors, whereas mosapramine, haloperidol, bromperidol and nemonapride had a slight to strong preference for D2- compared to 5-HT2A-receptors. In vivo, risperidone showed the highest potency for 5-HT2A-receptor occupancy; To obtain the same extent of D2-receptor occupancy, a 19-times higher dosage was required. 9-OH-Risperidone, the principal active metabolite of risperidone, showed a receptor occupancy profile comparable to that of risperidone. No regional selectivity for D2-receptor occupancy in mesolimbic vs nigrostriatal areas was detected for any of the compounds. Risperidone differed from the other compounds by the remarkably shallow slope of its D2-receptor dose-occupancy curve. A greater predominance of 5-HT2A-receptor vs D2-receptor occupancy and a more gradual occupancy of D2A-receptors differentiate risperidone from the other compounds. Both properties probably assist in preventing an extensive blockade of D2-receptors, the cause for extrapyramidal symptoms (EPS). The predominant 5-HT2A-receptor occupancy most likely underlies risperidone''s beneficial effects on the negative symptoms of schizophrenia and an adequately low D2-receptor occupancy adds to the treatment of positive symptoms with a low liability of EPS.
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  • Yukio Fujino, Tomoko Fujii
    1995 Volume 69 Issue 4 Pages 413-420
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    It has been well-established that insulin-induced hypoglycemia evokes preferential adrenaline release from the adrenal medulla in fasted adult rats. The present study examined the responsiveness to hypoglycemia in fasted 21-day-old and 8-week-old rats. The recovery of adrenaline in the chromaffin granule fraction prepared from the 8-week-old rat adrenal homogenate decreased 30 min after subcutaneous injection of 3 U/kg insulin, whereas the recovery of both adrenaline and noradrenaline was diminished in 21-day-old rats. In electron microscopy, Q-shaped profiles, indicative of exocytosis, were frequently observed in adrenaline- and noradrenaline-storing cells of 21-day-old rats. These results indicate that the responsiveness of the noradrenaline-storing cells to hypoglycemia in 21-day-old rats is different from that in young adult rats.
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  • Noriko Yamamoto, Koichi Yokota, Mikio Yoshidomi, Akira Yamashita, Mino ...
    1995 Volume 69 Issue 4 Pages 421-428
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The protective effect of KBT-3022 (ethyl 2-[4, 5-bis-(4-methoxyphenyl)thiazol-2-yl]pyrrol-1-ylacetate), a new cyclooxygenase inhibitor, in cerebral hypoxia and ischemia was studied and compared with those of indomethacin and acetylsalicylic acid (ASA). Oral administration of KBT-3022 (3-100 mg/kg) and indomethacin (3 and 10 mg/kg) significantly prevented KCN-induced death in mice, while ASA (100 mg/kg) had no effect. KBT-3022 (3 and 10 mg/kg, p.o.) and indomethacin (10 mg/kg, p.o.) significantly prolonged the survival time of mice subjected to normobaric hypoxia, while ASA (100 mg/kg, p.o.) had no effect. KBT-3022 (3-30 mg/kg, p.o.) and indomethacin (3 mg/kg, i.p.) significantly ameliorated delayed neuronal death in the gerbil hippocampal CAI sector after occlusion of bilateral carotid arteries for 5 min, while ASA (300 mg/kg, p.o.) had no effect. KBT-3022 (10 mg/kg, p.o.) significantly inhibited ATP depletion in the gerbil hippocampus after a 1-min occlusion of bilateral carotid arteries, but had no effect on ATP depletion after a 5-min occlusion and the recovery during recirculation. These results show that KBT-3022 exerts protective effects against cerebral anoxia and hypoxia and ameliorates delayed neuronal death in the hippocampus. KBT-3022 may therefore be useful for prophylaxis of ischemic cerebrovascular disorders.
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  • Atsushi Tomaru, Yasuhiro Ina, Nobuyuki Kishibayashi, Akira Karasawa
    1995 Volume 69 Issue 4 Pages 429-433
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The effects of adenosine and its related compounds on the cholinergic twitch response were examined in electrically stimulated guinea pig ileum. Adenosine (3 x 10-7-10-5 M) and an adenosine A1-receptor agonist N6-cyclohexyladenosine (CHA, 10-8-10-6 M) suppressed the twitch. Conversely, the A2a receptor agonist 2-[p-(2-carboxyethyl)phenethylamino]-5’-N-ethylcarboxamidoadenosine (CGS 21680, 10-9-10-7 M) potentiated the twitch in half the preparations examined. The A1-antagonist 1, 3-dipropyl-8-cyclopentylxanthine (DPCPX), which per se did not affect the twitch, recovered the attenuated twitch caused by CHA (10-7 M) or adenosine (10-6 M) and converted it into a potentiated twitch. These results suggest the presence of adenosine A1- and A2a-receptors coupled negatively and positively, respectively, to acetylcholine release in the preparation.
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  • Toshihiko Kaise, Kenji Ohmori, Yasuo Sakakura, Kotaro Ukai
    1995 Volume 69 Issue 4 Pages 435-438
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    We investigated the effect of KW-4679 (Z-11-(dimethylaminopropyliden)-6, 11-dihydrodi-benzoxepin-2-acetic acid hydrochloride), an antiallergic agent, on the nasal blockage induced by antigen challenge into the nostrils of actively sensitized guinea pigs. The change of the nasal cavity volume caused by nasal mucosal swelling after antigen challenge was measured by acoustic rhinometry. Oral administration of KW-4679 (0.01-10 mg/kg) significantly inhibited the decrease in the nasal cavity volume at 10 min, 30 min and 6 hr after antigen challenge. Ketotifen (1-10 mg/kg, p.o.) also inhibited the decrease in the nasal cavity volume after antigen challenge. These results indicate that KW-4679 may be useful for the treatment of allergic rhinitis.
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  • Kam-Ming Ko, Duncan H.F. Mak, Pui-Chun Li, Michel K.T. Poon, Siu-Po Ip
    1995 Volume 69 Issue 4 Pages 439-442
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    Exposure of liver homogenates to an in vitro tert-butyl hydroperoxide challenge can be used as a means for measuring the reduced glutathione regeneration capacity (GRC) of hepatic tissues. Pretreatment of rats with a lignan-enriched extract of Fructus Schisandrae (FS) caused a moderate enhancement of hepatic GRC in control rats, but the GRC enhancing effect of FS pretreatment on hepatic tissues was greatly exaggerated after CC14 challenge. This in vitro bioassay can be used for investigating the hepatic GRC promoting action of orally active agents.
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  • Katsuhiro Fujimoto, Keiko Yamamura, Tetsuo Hayashi, Takashi Osada, Tsu ...
    1995 Volume 69 Issue 4 Pages 443-445
    Published: 1995
    Released: April 07, 2006
    JOURNALS FREE ACCESS
    The susceptibility of Dacron grafts to infection is compared with Dacron grafts applied with levofloxacin-bonded albumin (LVFX-ALB) following the inoculation of 107 cells Staphylococcus aureus in rats. Staphylococcus epidermidis was inoculated in the same manner. While the control grafts were infected at the time of removal, the LVFX-ALB Dacron grafts resisted infection, thus demonstrating their effectiveness.
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