Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 88, Issue 5
Displaying 1-9 of 9 articles from this issue
  • Toshitaka NABESHIMA, Akira KATOH, Tsutomu KAMEYAMA
    1986 Volume 88 Issue 5 Pages 331-337
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    A behavioral method, using a shuttle box (one of the conditioned behaviors) for assessing visual function in mice, was investigated. Normal ICR mice were trained to avoid the unconditioned stimulus (electric footshock) during the presentation of conditioned stimuli (tone and light). After acquisition of avoidance response, normal ICR mice were presented randomly tone or light as the conditioned stimulus. The percent of avoidance in the presentation of light was decreased suddenly, but that of tone was not. However, the decrease of avoidance response to light stimulus was recovered by following trainings. The mice, which had acquired the condition response to tone and light stimulus alone, were treated in their cornea with 4N NaOH. The decrease of percent of avoidance in the mice with alkali-treated cornea after differentiation of conditioned stimuli did not recover following training. These results suggested that visual impairment of mice can be detected by this method. Therefore, we attempted to detect the visual impairments of dominant (Cts) and recessive (cac) hereditary cataract mice, hereditary retina degenerated mice (C3H) and first filial generation mice of C3H, F1 [(ICR×C3H)F1]. The acquisition curves of both Cts and cac cataract mice were similar to that of normal ICR mice, but those of C3H and Fl were similar to that of ICR mice treated with alkali. Moreover, changes in recovery %, which was calculated from avoidance response in the presentation of light alone after differentiation of conditioned stimuli, corresponded to the above results. These findings demonstrated that the visual impairment of Cts and cac cataract mice is weak, while that of C3H and F1 mice is strong.
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  • Pharmacological comparison between (6)-shogaol and capsaicin
    Mamoru SUEKAWA, Hideko SONE, Iwao SAKAKIBARA, Yukinobu IKEYA, Masaki A ...
    1986 Volume 88 Issue 5 Pages 339-347
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Pharmacological actions of (6)-shogaol and capsaicin were studied. Both (6)-shogaol (0.5 mg/kg, i.v.) and capsaicin (0.1 mg/kg, i.v.) caused a triad such as a rapid fall in blood pressure, bradycardia and aponea in rats. Both drugs-induced marked pressor responses in blood pressure, which occurred after the rapid fall, were markedly reduced by a spinal destruction. In pithed rats, both drugs-induced peripheral pressor responses were markedly reduced with the combined treatment of [D-Arg1, D-Pro2, D-Trp7, 9, Leu11]-substance P (0.5 mg/kg, i.v.), phentolamine (10 mg/kg, i.v.) and the section of sciatic nerves. In isolated guinea-pig trachea, (6)-shogaol (100 μM) and capsaicin (10 μM) induced contractile responses which were slightly inhibited by substance P antagonist (10 μM), but exhibited also a tachyphylaxis. Furthermore, although (6)-shogaol (3.6 μM) showed positive inotropic and chronotropic actions on isolated atria in rats, this effect of (6)-shogaol disappeared by repeated injections or pretreatment (100 mg/kg, s.c.) of (6)-shogaol. These results suggest that (6)-shogaol and capsaicin have similar actions, and that both drugs may cause a peripheral action by releasing an unknown active substance from nerve ends.
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  • Masao HISADOME, Yuko NAKAMURA, Takeki OKUMOTO, Kiyoteru IKEGAMI
    1986 Volume 88 Issue 5 Pages 349-354
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The production of hemolytic plaque forming cells (HPFC) in the spleen of BALB/c mice immunized with sheep red blood cells was significantly inhibited by carrageenan treatment(0.3 mg/kg, i.p.; on days −3 and −1). Cysteine ethylester hydrochloride (ethylcysteine) restored the inhibition of the HPFC production by carrageenan treatment in a dosedependent manner (10 ?? 100 mg/kg, p.o.). Ia positive cells (antigen-presenting cells) increased in the spleen adherent cells (SAC) obtained from immunized mice, whereas they decreased in the SAC obtained from carrageenan-treated mice. An increase of la positive cells occurred in the SAC of carrageenan-treated mice given ethylcysteine. Ethylcysteine (10 ?? 100 mg/kg, p.o.; on days −2 and −1) prevented both the suppression of the HPFC production and the decrease of the number of thymus lymphocytes and peripheral leukocytes induced by cyclophosphamide treatment (30 mg/kg, i.p.; on days −1 and 0). Lyt 1.2 positive cells (helper T cells) decreased in the spleen T cells of cyclophosphamide-treated mice, but increased in the spleen T cells from cyclophosphamide-treated mice give ethylcysteine. On the other hand, Thy 1.2 negative cells (B cells) did not increase in the spleen cells of cyclophosphamide-treated mice with or without ethylcysteine. These results suggest that ethylcysteine restores the immune response in immunosuppressed mice through the functions of macrophages and/or helper T cells.
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  • Kouji MORIKAWA, Toshie YAMAUCHI, Hideo KATO, Yasuo ITO
    1986 Volume 88 Issue 5 Pages 355-361
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The effects of FL-155, which was synthesized to develop a new orally-active anti-pollakiuria agent, on the rhythmic bladder contractions were studied in anesthetized rats. At a pressure exceeding 10 cm H20 in the bladder, a rhythmic bladder contraction was observed up to at least 120 min. This response was abolished by a spinal (C1 level) cut, cuts of both pelvic nerves, thiopental (3.0 mg/kg, i.v.) or lidocaine (1.0 mg/kg, i.v.); and atropine (0.01 mg/kg, i.v.) strongly inhibited the amplitude of the response. FL-155 and flavoxate, in intravenous (0.3 ?? 3.0 mg/kg and 1.0 ?? 3.0 mg/kg, respectively) and intraduodenal (12.5 ?? 100 mg/kg and 200 ?? 400 mg/kg, respectively) administrations, dose-dependently abolished the rhythmic bladder contractions, and FL-155 was 8.16 times more potent than flavoxate in intraduodenal administrations. These results suggest that the rhythmic bladder contraction in anesthetized rat may be a polysynaptic reflex through pelvic nerves and the central nervous system (supraspinal level), and FL-155 appears to be a candidate for an orally active anti-pollakiuria agent.
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  • Ameliorative effect on cerebral energy metabolic disorder induced by KCN
    Hiroshi YASUDA, Noriyoshi IZUMI, Masato NAKANISHI, Koretake ANAMI, Yut ...
    1986 Volume 88 Issue 5 Pages 363-367
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The amelioration of energy metabolic disturbance in cerebral anoxia is valuable for the treatment of various cerebral ischemic diseases and insufficiency. In this study, the effectof Y-8894 on the cerebral energy metabolism was investigated using a KCN-induced cerebral anoxia model with mice. The intravenous injection of a lethal dose of KCN (2.5 mg/kg) induced rapid and marked decreases of brain glucose, phosphocreatine and ATP contents, with a remarkable enhancement of lactate and AMP levels, indicating a severe disorder of the cerebral energy metabolism. This phenomenon was also shown by an irreversible deterioration of the energy charge potential (ECP), an index of the cerebral energy state. The treatment with Y-8894 (30 mg/kg, i.p.) remarkably ameliorated this KCN-induced energy metabolic disturbance: markedly reducing the changes in brain phosphocreatine, glucose and lactate contents, while keeping ATP, AMP and ECP at nearly their normal levels. In addition, these changes in the Y-8894 treated group recovered promptly to normal, whereas those in the control group were irreversible. In normal mice, Y-8894 induced a significant increase in the cerebral glucose content without affecting either the cerebral glycolytic metabolism or the energy state. The present findings suggest that Y-8894 has an ameliorative effect on the cerebral energy metabolic disturbance, and this effect likely plays an important role in the improvement of amnesia and other neurological deficits related to cerebral anoxia.
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  • Masao HISADOME, Yuko NAKAMURA, Takeki OKUMOTO, Kiyoteru IKEGAMI
    1986 Volume 88 Issue 5 Pages 369-374
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    ICR mice were treated orally with cysteine ethylester hydrochloride (ethylcysteine, 10 and 100 mg/kg) immediately before the intraperitoneal injection of yeast particles. This agent significantly potentiated phagocytosis of yeast particles by peritoneal polymorphonuclear leukocytes in mice obtained 2 hr after the yeast injection, and the treatment with this agent (3 and 30 mg/kg, p.o.) 4 hr before the injection of yeast potentiated phagocytosis of yeast particles by mouse peritoneal leukocytes. This agent (30 mg/kg, p.o.) restored the suppression of phagocytosis of mouse leukocytes by the intraperitoneal administration of cyclophosphamide (30 mg/kg, i.p.) 24 hr before the yeast injection. This agent (10 ?? 100 mg/kg, p.o.) had no effect on the decrease of peripheral leukocyte number in irradiated mice (560 rad), but restored the suppression of phagocytosis, nitroblue tetrazolium (NBT) reduction and stimulated NBT reduction by the addition of lipopolysaccharide. Furthermore, this agent (3 ?? 30 mg/kg, p.o.) potentiated phagocytosis, NBT reduction and stimulated NBT reduction of peripheral leukocytes obtained from guinea pigs 2 and 6 hr after ethylcysteinetreatment. It is suggested that ethylcysteine potentiates phagocytosis and NBT reduction of leukocytes in animals, and it restores phagocytosis and NBT reduction inhibited by the treatment with cyclophosphamide or X-ray irradiation. It may be possible that this stimulating effect of ethylcysteine could be at least in part involved in the stimulation of nonspecific resistance to infection in the compromised host.
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  • Determination of metabolites in monkey plasma by combined high-performance liquid chromatography and enzyme immunoassay
    Toshiro YAMAGUCHI, Meiko YAMASHITA, Koichi SUGENO
    1986 Volume 88 Issue 5 Pages 375-387
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    A new sleep-inducer, 450191-S, was orally administered to two old rhesus monkeys and three young ones at a pharmacologically active dose (1 mg/kg). The area under the plasma concentration versus time curve (AUC) of M-1 was the smallest among the measured metabolites. The AUC of M-2 in the old monkeys was 10 times higher than that of the young ones. M-A was one of the major metabolites, and its AUC in the old monkeys was also four times higher than that in the young ones. The AUC of M-3 was the largest among the measured metabolites. The time of maximum concentration was 12-16 hr after dosing; and thereafter, the concentration decreased gradually with a 12-hr half-life. The M-4 level was constantly low during 24 hr after dosing and then decreased gradually. The active metabolite M-1 was also administered to the two young monkeys at a dose of 0.73 mg/kg, and the time course of the plasma concentration of metabolites was compared with that after 450191-S administration to the young monkeys, because 450191-S may be changed to M-1 in the process of intestinal absorption. The concentration of M-1 was extremely low in spite of the dosing of M-1 itself, and the AUC of M-1 was one-sixth of that after 450191-S administration. The concentration of M-2 was also low, and its AUC was one-third of that after 450191-S administration. The AUC's of M-A, M-3 and M-4 were not very different from those after 450191-S administration. These results indicated that there is an age-related difference in the plasma concentration of M-2 and M-A when 450191-S is administered orally and that the plasma concentrations of M-1 and M-2 differ greatly between 450191-S and M-1 administrations.
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  • Hiroyuki SONOKI, Yasumi UCHIDA, Masatoshi MASUO, Takanobu TOMARU, Akih ...
    1986 Volume 88 Issue 5 Pages 389-394
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Forskolin is a diterpene of the labdane family which activates adenylate cyclase. The effects of forskolin were investigated in a congestive heart failure (CHF) model that we newly established using anesthetized dogs. The model was made by the intramural injection of protease into the left ventricular free wall, saline loading, and dextran and methoxamine infusion. By this maneuver, aortic blood flow (AoBF) was decreased; left atrial pressure (LAP), systemic vascular resistance (SVR) and left ventricular endodiastolic pressure (LVEDP) were markedly increased; and systemic blood pressure was unchanged. A bolus injection of 5.0 μg/kg forskolin reversed the hemodynamic findings of CHF. It reduced LAP (17.5→7.9 mmHg) (mean, N=7), SVR (19980→10390 dyne sec/cm5), time constant T (90.7→59.2 msec) and LVEDP (22.8→16.8 mmHg); and it increased Vmax (2.32→2.82 l/sec) and AoBF (0.50→0.72 l/min). Forskolin improved the CHF mainly through its vasodilator and positive inotropic actions.
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  • Shoji YAMADA, Tomio MOROHASHI
    1986 Volume 88 Issue 5 Pages 395-401
    Published: 1986
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effect of sodium salicylate (SS) on renal handling and plasma concentration of calcium (Ca), phosphate (Pi) and magnesium (Mg) was studied in over-night fasted rats. Hypophosphatemic hypocalcemia was observed after the administration of 200 mg/kg of SS; on the other hand, hypermagnesemia was induced only with the dose of 400 mg/kg. A clearance study with the smaller dose of SS showed a decrease in urinary flow rate; however, the glomerular filtration rate remained unchanged. Reduction of urinary Ca excretion which was mainly due to a decreased filtered load was observed. On the other hand, we observed increased urinary excretion of Pi and decreased Mg excretion, which resulted from the changes in tubular reabsorption of Pi and Mg, respectively. It was concluded that the administration of SS caused 1) a hypocalcemia by the action on a tissue other than the nephron, followed by a decreased filtered load, then a reduction of urinary Ca excretion. 2) a decreased tubular reabsorption, which contributes to hypophosphatemia. 3) However, the temporary increase in tubular reabsorption of Mg makes only a small contribution to the hypermagnesemia. It was suggested that an inhibition of cyclooxygenase was not related to these effects of salicylate on renal handling of these electrolytes.
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