Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 74, Issue 8
Displaying 1-9 of 9 articles from this issue
  • Takao OSHIMA, Yuji MARUYAMA
    1978 Volume 74 Issue 8 Pages 885-895
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Catecholamines are neurotransmitters produced and secreted by the central and autonomic nervous systems. In addition to being neurotransmitters, amines produced mainly by the adrenal medulla also act as hormones. Fluorometric measurements of amines yield variable results because of the poor sensitivity of the techniques, and the low concentration of these amines in tissues and biological fluids. The lack of specific and sensitive analytical methods has been an obstacle to resolving the mechanism of action of these neurotransmitters and hormones. The possibility of achieving qualitative and quantitative determination of picomole or femtomole amounts of these amines is a major need. Recently, radioenzymatic procedures for catecholamine assay have been developed and there has been a significant improvement in both sensitivity and accuracy of catecholamine assays. In this article, details of these radioenzymatic assay methods are reviewed.
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  • The anti-ulcer effects of isoprenyl chalcone extracted from sophora subprostrata
    Michitada SASAJIMA, Sadao NAKANE, Ryuichi SAZIKI, Hideo SAOTOME, Katsu ...
    1978 Volume 74 Issue 8 Pages 897-905
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    A series of extracted fractions from sophora subprostrata was screened by determining anti-ulcer effects in pylorus ligated and stressed rats. Fr. [C-2] had the most potent anti-ulcer effects of all fractions extracted. Sophoradin and sophoranone which were isolated from Fr. [C-2] were also found to have inhibitory effects on ulcer formation in pylorus ligated and stressed rats. The anti-ulcer effect of sophoradin was relatively potent in comparison with that of sophoranone and/or Fr.[C-2].The anti-ulcer effect of sophoranone was approximately the same as that of Fr.[C-2].The authors examined the effects of sophoradin and sophoranone on gastric secretion in pylorus ligated rats. Sophoradin and sophoranone significantly reduced the volume of gastric juice. Sophoradin but not sophoranone inhibited the free and total acid output of gastric juice. The effect of sophoradin was examined on various secretagogues which induced gastric secretions in rats with acute fistula. Sophoradin showed a tendency to inhibit tetragastrin and insulin-induced gastric acid secretion, but there were no effects on methacholine and histamine-induced secretions. These results suggest that sophoradin may have marked anti-ulcer and inhibitory effects on gastric secretion.
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  • Tumor immunity
    Hiroshi MORI, Ikuo SAIKI, Akihide KODA
    1978 Volume 74 Issue 8 Pages 907-923
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    E.L.4 lymphosarcoma (E.L.4) s.c. as a syngeneic tumor was transplanted into C57BL/6 mice, 4 weeks old. The tumor growth was more rapid in male mice. An i. p. injection of α-MPG or DPA caused a decrease of the tumor growth and prolongation of the survival time in male mice. In contrast, an acceleration of the growth and a reduction of the survival time were observed in females dosed with α-MPG or DPA. Such a sexual difference and the activity of drugs decreased with the progress of age. α-MPG and DPA had little effect on the number of recovered and living E.L.4 cells in vitro. However, with the inoculation of α-MPG-treated E.L.4 into mice, the tumor rapidly grew in a dose dependent manner. On the other hand, there was a tendency toward suppression of the tumor growth when DPA was given. Development and growth of tumor in mice induced by 20-methylcholanthrene showed a tendency toward suppression in male mice when α-MPG in a dose of 5 mg/kg was given every other day, and in both sexes with the same dose of DPA. Responses of spleen and lymph node cells to phytohemagglutinin-P (PHA) or lipopolysaccharide (LPS) were reduced by the transplantation of E.L.4 in 4 week old mice. With α-MPG and DPA a reduction in PHA response of both the cells tended to recover, and that in LPS response of lymph node cells was recovered. In these mice, the decrease in cytotoxicity of spleen and lymph node cells agianst E.L.4 was recovered by treatment with both drugs. There was also a complement-dependent cytotoxicity against E.L.4 in their sera, and the activity was further increased by the administration of α-MPG. These findings suggest that α-MPG and DPA are anti-tumor agents which act through immune mechanisms.
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  • Toshio SUGA, Masami SUZUKI
    1978 Volume 74 Issue 8 Pages 925-940
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Actions of cardiac steroids (CS) such as bufadienolides and cardenolides, on guinea pig taenia coli were studied using the double sucrose-gap method. When an appropriate dose of CS was applied, the taenia coli first contracted, then relaxed. After removal of CS, the relaxation was enhanced and continued for 20-40 min. In decreasing order of the relaxant action were bufalin, ouabain, cinobufagin and resibufogenin. Further application of CS after occurrence of the relaxation induced a secondary gradual contraction. The contraction occurred with the membrane depolarization and increase in spike discharge, and the relaxation corresponded fairly well with decrease in spike discharge and the membrane repolarization. Membrane resistance was decreased during the contraction as well as the relaxation. The decrease in membrane resistance continued during the relaxation after removal of CS. Na, K and Ca conductances were increased by CS application, respectively. The increase of Na conductance was relatively high during the contraction, and the increase of K conductance was remarkable during the relaxation and after removal of CS. From the foregoing results it is considered that the contracting action is due to inhibition of the Na pump and that the relaxant action is due to the change in electrical properties of membrane produced by a marked increase in intracellular Na and the increase of K permeability. The relaxation after removal of CS is considered to be due to the activated electrogenic Na pump as indicated from the changes in electrical properties of membrane.
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  • Kazuo HASEGAWA, Minoru TANAKA, Hideyuki KOBAYASHI, Masataka KIKUNO
    1978 Volume 74 Issue 8 Pages 941-950
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    In an analysis of the gastrocnemius muscle, the microsomal fraction showed the highest cholinesterase (ChE) activity. The ChE activity of all fractions decreased to a greater extent after strong nerve crushing than after weak crushing. This change in the activity in the microsomal fraction was the most marked change observed.Although in the analysis of the coleus muscle the ChE activity was measured only in the homogenate and in the microsomal fraction, the results were the same as those obtained with the gastrocnemius. A preparation of vitamins B1, B6, and B12 (B complex) had little effect on the ChE activity in the gastrocnemius muscle. In the soleus muscle on the lesion side, the B complex increased the ChE activity to some extent after nerve crushing, but such was not significant. However, the B complex significantly increased this activity in the soleus on the intact side. In the soleus muscle, strong nerve crushing induced more marked muscle atrophy than weak crushing. On the other hand, no significant difference was found in the gastrocnemius. Effects of the B complex on muscle atrophy were found in the soleus, but not in the gastrocnemius. These results suggest that the ChE activity in the microsomal fraction containing sarcoplasrnic reticulum reflects the nervous disorder clearly, and that the B complex increases the ChE activity and muscle weight in the soleus, but not in the gastrocnemius muscle.
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  • Haruo NAGAYAMA, Akinori TAKAGI, Yukihiko SAKURAI, Seishi YOSHIMOTO, Ke ...
    1978 Volume 74 Issue 8 Pages 951-957
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Rats were given haloperidol in a variety of doses and time combinations and the sedation period were then measured. A clear-cut daily fluctuation in the sedative effect was observed, and the pattern of fluctuation differed depending on the dosage. In an attempt to elucidate the mechanism of this phenomenon, haloperidol was administered at two different times between which there was a significant difference in the sedation period. No difference was found. Thus it is presumed that daily fluctuation in the sedative effect of haloperidol may be ascribed not to the daily fluctuation in the levels of absorption, excretion, metabolism, or distribution of this drug, but rather to the daily fluctuation at the level of catecholamine receptors in the brain. There was a daily fluctuation in the antiapomorphine effect of haloperidol in a variety of doses and time combinations, and the pattern of fluctuation almost equaled that of the sedative effects of haloperidol. The daily fluctuation of the sedative effect is probably due to effects of circadian rhythm in brain dopamine receptors.
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  • Takashi MITSUSHIMA, Showa UEKI
    1978 Volume 74 Issue 8 Pages 959-979
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Behavioral effects of Flutazolam (MS-4101), a new derivative of benzodiazepines, was investigated and compared with effects of diazepam in mice and rats. MS-4101 suppressed hyperemotionality in septal rats, fighting behavior in long-term isolated mice and pentylenetetrazol convulsion and potentiated thiopental sleep. These effects of MS-4101 were the same in potency as those of diazepam. MS-4101 was more potent than diazepam in reducing the spontaneous locomotor activity in the open-field test and potentiating the stimulant effect of methamphetamine on locomotor activity. On the other hand, suppression of hyperemotionality in O. B. rats, potentiation of ethanol-induced anesthesia, prevention of maximal electroshock, prevention of strychnine convulsin and muscle relaxant effect of MS-4101 were less potent than in the case of diazepam. MS-4101 had also an anticonflict effect, which was less potent than that seen with diazepam. Suppression of locomotor activity was potentiated by chronic administration of MS-4101, but disappeared with chronic administration of diazepam. MS-4101 inhibited considerably both scratching and head-twitch induced by mescaline in mice. Scratching was increased with small doses of diazepam and decreased with high doses. Head-twitch was decreased with small doses of diazepam and increased with high doses.
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  • Yoshikazu YANAGI, Hiroshi KUROKAWA, Yasuko NAGAO, Toshiya INUKAI
    1978 Volume 74 Issue 8 Pages 981-990
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    Antipyretic activity of SL-573 was not influenced by age and sex difference in rats. The combined effect of other drugs on antipyretic activity of SL-573 was examined, using several drugs which might be clinically applicable. Cefazolin sodium, ampicillin sodium, codeine phosphate, hydrochlorothiazide and haloperidol did not show any significant effect on antipyretic activity of SL-573. Diazepam itself showed antipyretic activity, and its combined use with SL-573 resulted in an additive effect. SL-573 also showed antipyretic activity in mice with fever induced by yeast, as was seen in rats. SL-573 diminished the hyperthermic response to bacterial endotoxin and leucocytic pyrogen in rats, but not to 2, 4-dinitrophenol. Additionally, SL-573 did not inhibit the bacterial endotoxin-induced production of leucocytic pyrogen and its release in saline medium. SL-573, therefore, is considered to be a centrally acting antipyretic. Intraventricular injection of prostaglandin E2 and arachidonic acid induced a hyperthermia in mice. SL-573 clearly inhibited arachidonic acid-induced hyperthermia, but not prostaglandin E2-induced hyperthermia. Since SL-573 is known to inhibit prostaglandin biosynthesis from arachidonic acid, the prostaglandin biosynthesis inhibition may be one of the main mechanisms of antipyretic action of SL-573.
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  • Emiko OGUCHI, Masako OKAZAKI, Reiko HOBARA, Yoshie TOYOSHIMA, Koji SAK ...
    1978 Volume 74 Issue 8 Pages 991-1004
    Published: 1978
    Released on J-STAGE: March 29, 2007
    JOURNAL FREE ACCESS
    We observed under light and electron microscopes morphological changes in the brains of rats in a thiamine deficient state as induced by an oxythiamine, pyrithiamine and thiamine deficient diet (OT, PT and TDD). We simultaneously determined thiamine levels in the whole brain of rats. The rats were separated into six groups-normal control, OT or PT treated rats (OT or PT group), OT or PT treated rats fed a TDD (OTD or PTD group), rats fed a TDD (TDD group)-. Microscopically, there were symmetrically distributed lesions containing spongy reticulation mainly in the vestibular nucleus. Electron microscopically, we found more advanced lesions in the OTD and PTD groups than in the TDD group. These ultrastructural changes were seen in the vicinity of capillaries and such consisted of abnormal endothelial cells and pericytes, excrescence of microglias, swelling or vacuolation of astrocytes, nerve cells containing distorted organelle and myelin degeneration, besides extracellular edema. The thiamine level in the TDD group decreased to 56% that of control. No effect of OT on the thiamine level was observed either in case of ingestion of a regular diet or when TDD was given. On the other hand, the thiamine level decreased to 43% in the PT group and to 17-23 in PTD. These results suggest that encephalopathy caused by the OT or PT-induced thiamine deficiency has the same selective vulnerable site as does the TDD-induced deficiency, however cellular sensitivity may differ slightly with the various ultrastructural changes.
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