The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 25, Issue 3
Displaying 1-18 of 18 articles from this issue
  • Tadashi TAKEWAKI, Osamu YAGASAKI, Iwao YANAGIYA
    1975 Volume 25 Issue 3 Pages 223-232
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of distension of the intestinal wall on the liberation and the synthesis of acetylcholine (ACh) were studied in the isolated guinea-pig ileum measuring the changes in the amount of free and bound ACh. In the presence of eserine longitudinal distension increased the amount of bound ACh in the intestinal wall without increasing the free ACh, while circumferential distension or mucosal rubbing increased free but not bound ACh. These effects were evident within 30 sec. In the eserine-free medium the amount of bound ACh was increased in either direction of distension. Addition of more than 5×10-8g/ml ACh to the bathing medium completely blocked the distension-induced increase. It is concluded that the release and the synthesis of ACh may be both augmented by the circumferential and the longitudinal distension in the physiological conditions. In the presence of eserine, however, the presence of unphysiologically high extracellular ACh levels presumably inhibits the distension-induced augmentation of ACh synthesis in the tissue.
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  • Munekazu GEMBA, Kenjiro YAMAMOTO
    1975 Volume 25 Issue 3 Pages 233-240
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effect of inorganic phosphate (4×10-3 M) on Ca++-accumulation was examined in kidney cortex mitochondria. Ca++-accumulation of rat kidney cortex mitochondria was slightly influenced by inorganic phosphate. On the other hand, dog kidney cortex mitochondria did not accumulate calcium from the incubation medium until the inorganic phosphate had been added. Ca++-accumulation of rabbit kidney cortex mitochondria was markedly stimulated by inorganic phosphate. When ethacrynic acid was added to the reaction medium in the absence of inorganic phosphate, Ca++-accumulation of rat kidney cortex mitochondria was depressed and the decrease in calcium content of rabbit and dog kidney cortex mitochondria was enhanced. In the presence of inorganic phosphate, the inhibition of Ca++-accumulation by ethacrynic acid was observed only on dog kidney cortex mitochondria. Subsequently, the effect of inorganic phosphate (4×10-4 M) and ethacrynic acid (1×10-4 M) on Ca++-ATPase was examined in kidney cortex mitochondria. The low concentration of inorganic phosphate (4×10-4 M) activated Ca++-ATPase of kidney cortex mitochondria in all animal species. The greatest activation of Ca++-ATPase occurred in rabbits, but the activity of the enzyme was lower than that in rats and dogs. Inhibition of Ca++-ATPase by ethacrynic acid was depressed by the addition of inorganic phosphate in kidney cortex mitochondria of experimental animals. Ca++-accumulation may be regulated through the stimulating effect of inorganic phosphate and the inhibitory effect of ethacrynic acid on Ca++-ATPase in kidney cortex mitochondria. Species difference in ethacrynic acid effect on Ca++-accumulation in kidney cortex mitochondria of rats, rabbits and dogs is discussed.
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  • Nobuo NAKAMURA, Shizuo SHIOZAKI, Yoshihisa KOYAMA, Tetsuo KOJIMA, Hiro ...
    1975 Volume 25 Issue 3 Pages 241-250
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    With low doses of caerulein given intravenously or subcutaneously, vomiting could be induced. Although vomiting was not inhibited by chlorpromazine or atropine, a strong inhibition was evident when metoclopramide was administered subcutaneously at such doses as inhibit vomiting induced by oral administration of CuSO4. Even high doses of caerulein failed to induce vomiting in vagotomized and splanchnicotomized dogs. With intraventricular injection, no effects were observed on blood pressure, respiration or gastrointestinal motility, and vomiting was not induced. Therefore, a reflex mechanism appears to be involved in vomiting induced by caerulein. It is suggested that the actions of caerulein may not be mediated through the central nervous system.
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  • Gianni BENZI
    1975 Volume 25 Issue 3 Pages 251-261
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The behaviour of (a) the redox potential of the lactate/pyruvate system and the changes of the redox potential of the lactate/pyruvate system across the brain; (b) the energy charge potential of the adenylate pool, was studied in the brain of curarized beagle dogs. The influence of certain drugs (amobarbital, nicergoline, theophylline, papaverine, bamethan, dipyridamole, bemegride) on these parameters was evaluated under control conditions, during hypoxemia and during post-hypoxiemic recovery. On the whole, the action on energetic metabolism appears to be unrelated to the action believed to be exerted by drugs on cerebral vessels.
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  • Norio SATO, Yoshio UENO, Makoto ENOMOTO
    1975 Volume 25 Issue 3 Pages 263-270
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Acute and subacute toxicities to cats of T-2 toxin, 12-13 epoxytrichothec mycotoxin from fungi Fusarium species and others, were investigated. Major symptoms of toxicity in cats as the result of T-2 toxin were emesis, vomiting, diarrhea, anorexia, ataxia of the hind legs, discharge from the eyes and ejection of hemorrhagic fluid. Consecutive administration of the crude and pure sample of T-2 toxin in a sublethal dose caused a marked decrease in the number of circulating white blood cells. In the early stage of intoxication, a temporal leukocytosis was observed after each administration. Autopsy revealed extensive cellular damages in the bone marrow, intestine, spleen and lymph nodes. Greatly evident were meningeal hemorrhage of the brain, bleeding in the lungs and vacuolic degeneration of the renal tubles. Mycotoxicological significance of T-2 toxin and related trichothecenes is discussed in relation to the food-borne diseases in humans and farm animals.
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  • Yasuko KOSHIHARA, Mieko YAMAGISHI, Sei-itsu MUROTA, Susumu TSURUFUJI
    1975 Volume 25 Issue 3 Pages 271-280
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Cortisol-binding protein was prepared and partially purified by (NH4)2SO4 fractionation and DEAE-cellulose column chromatography from 105, 000 g supernatant fraction of cytoplasm in rat carrageenin granuloma, which is assumed to be one of the most appropriate experimental models of inflammation. The cortisol-binding protein in the inflammatous tissue, although similar to transcortine, was not transcortine itself. The binding protein was eluted at 0.12 M NaCl by DEAE-cellulose column chromatography with a shallow salt gradient. Sedimentation constant and dissociation constant of the binding protein were 4-5 S and 1.0×10-9 M, respectively. Optimum pH for binding to cortisol was 8.0. Binding ability of the binding protein to cortisol was very sensitive to pronase E and trypsin but resistant to RNase. Specificity of the protein for binding other steroids revealed that 17β-estradiol did not bind to the protein, while androstenedione and testosterone had one sixth as much affinity to the binding protein as that of cortisol. There was good a correlation between the amount of the binding protein in the inflammatory tissue and anti-inflammatory effect of cortisol. Namely, the maximum cortisol-binding ability was seen on a 5 day old granuloma which is the so called `steroid sensitive stage'. Thereafter, the binding ability decreased with the increasing stage of granuloma.
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  • Taku NAGAO, Sakae MURATA, Masanori SATO
    1975 Volume 25 Issue 3 Pages 281-288
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effect of diltiazem (CRD-401) on coronary collaterals was studied in the dog. The anterior descending branch of the left coronary artery was occluded for 4 to 6 weeks by an ameroid constrictor. In these dogs, the retrograde flow (RF) from the peripheral coronary artery and peripheral coronary pressure (PCP) were significantly higher than those in acute coronary-ligated dogs, suggesting the development of large supraepicardial intercoronary anastomoses. Diltiazem (100 μg/kg i.v.) increased circumflex blood flow (CBF) for several min, while nitroglycerin (10 μg/ kg i.v.) increased CBF transiently after which CBF decreased to below control values. Diltiazem (100 μg/kg) and nitroglycerin (10 μg/kg) increased RF/MAP (mean aortic pressure) and PCP/MAP and these increases lasted longer than that of CBF. Diltiazem also increased RF in doses of 100 μg/kg or 20 μg/kg/min. Therefore, diltiazem possesses the property of dilating coronary collaterals thus causing redistribution of intramyocardial blood flow. In acute preparations, however, both diltiazem and nitroglycerin showed no significant changes in PCP/MAP and RF/MAP.
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  • Isao NEGISHI, Yoshio AIZAWA
    1975 Volume 25 Issue 3 Pages 289-294
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of orotic acid on liver lipid accumulation and incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein, and into serum beta-lipoprotein were studied. Male and female rats of Wistar strain were fed a semisynthetic diet supplemented with 1 per cent orotic acid for 7 days. Feeding of orotic acid induced a marked fatty liver in female rats, but not in males. In female rats, radioactivity in liver phosphatidylcholine was significantly decreased by orotic acid, and that in liver protein was slightly decreased. In male rats, incorporation of methionine [methyl-14C] into liver phosphatidylcholine and protein was unchanged between the control and the rats fed orotic acid. Radioactivity in serum beta-lipoprotein was decreased to a greater extent in female rats than in males. These results suggest that sex difference in the development of fatty liver may be due to the difference in the effect of orotic acid on liver phosphatidylcholine biosynthesis.
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  • Shiro MORIMOTO, Kuniaki TANAKA, Ryoko KITANO
    1975 Volume 25 Issue 3 Pages 295-301
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Subcellular localization of renin in the rabbit kidney cortex was investigated using two centrifugation techniques. Renin was indirectly assayed on the basis of pressor activity and the reference enzymes such as succinic dehydrogenase, acid phosphatase and D-glucose-6-phosphatase for the other subcellular particulates were biochemically determined. Renin activity was found mainly in the mitochondrial fraction with very little in the microsomal fraction by a differential centrifugation. By a discontinuous sucrose density gradient centrifugation, renin granules were mainly recovered in the fraction corresponding to 1.5 M sucrose, while most of mitochondria, lysosomes and microsome equilibrated in the upper fractions. This resin granular fraction contained approximately 50% of total granular renin activity having a specific activity about six times that seen in the homogenate. After recentrifugation of the resin granular fraction, most of resin activity was recovered in the sediment. Repeated freezing and thawing of this fraction resulted in an increase of renin activity. On the basis of these experimental data it is assumed that renin located in the different subcellular particulates from mitochondria, lysosomes and microsomes in the rabbit kidney cortex.
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  • Heitaroh IWATA, Hiroshi OKAMOTO, Setsuko KOH
    1975 Volume 25 Issue 3 Pages 303-310
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Various drugs known to bind to serum albumin were examined to determine whether or not they influenced the level of free tryptophan in serum in vitro and in vivo. Possible relationships between the serum free tryptophan level and scrotonin (5-HT) synthesis in the brain and the hypothermic effects of these drugs were investigated. Of the drugs examined, sodium salicylate, sodium benzoate and indomethacin caused a significant increase in the concentration of serum free tryptophan and stimulated the synthesis of 5-HT in the brain. Hypothermia induced by salicylate and indomethacin was potentiated by pretreatment with pargyline, a monoamine oxidase inhibitor. Administration of benzoate did not cause any change in body temperature, but after pargyline a hypothermia did occur. However, pretreatment with parachlorophenylalanine, an inhibitor of 5-HT synthesis, did not influence the hypothermia induced by salicylate and indomethacin. Relationship between the hypothermic effect and the increase of 5-HT synthesis in the brain after a large dose of salicylate and indomethacin is discussed.
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  • Junzo SASAKI
    1975 Volume 25 Issue 3 Pages 311-324
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Alpha-chymotrypsin (CT) was modified chemically and physically by the treatments with diisopropyl fluorophosphatc, L-(1-tosylamide-2-phenyl) ethylchloromethylketone, hydrogen peroxide and heat. After these treatments, CT lost or decreased both the enzymic activity and ability of releasing histamine from rat mast cells. Ca++ was essential for histamine release by CT, while it enhanced only slightly the enzymic activity. Process of histamine release by CT could be separated into two stages: CT-dependent but not Ca++-dependent, and Ca++-dependent but not CT-dependent. The activated state of mast cells produced by CT decayed rapidly at 37°C in the absence of Ca++, but these cells responded to Ca++ by adding CT once again, suggesting reconstitution of cell membrane structure affected by CT. Isoproterenol, epinephrine, prostaglandin E, , and dibutyryl-cyclic AMP (0.01-0.1 mM) did not inhibit release of histamine induced by CT. Neither theophylline (0.01-0.1 mM) alone nor the combinations of these cyclic AMP-active agents with theophylline inhibited the release of histamine. But, in the presence of papaverine (0.01-0.1 mM) a marked, dose-dependent inhibition was observed. These data suggest that 1) release of histamine by CT from rat mast cells is causally related to its hydrolytic activity, 2) this activity causes a reversible change on mast cell membrane which probably facilitates Ca++-influx through the cell membrane, and 3) there are subtle differences among CT, compound 48/80 and antigens concerning the effect of cyclic AMP-active agents in histamine-releasing mechanisms in mast cells.
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  • Tsutomu NODA, Kazunori ARAKI, Masao KOIDA, Hiroshi KANETO
    1975 Volume 25 Issue 3 Pages 325-333
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    How closely the isolated liver of the rat would simulate the in vivo function of the organ in terms of the metabolic pattern of the compounds such as bromosulphophthalein, ρ-nitrophenol, hexobarbital, and indocyanine green was investigated. In order to produce tissue with the stimulated function, the animal was pretreated with phenobarbital and, for the reverse purpose, with ethionine. Some of the indices of the function employed herein, such as the appearance pattern of the compound, the rate of biochemical transformation or the biliary excretion, showed that the perfused liver would generally well reflect the in vivo situation. The method with isolated and perfused liver could exclude the participation of other organs and also the influence of the factors unavoidable in an in vivo experiment. Thus, it is suggested that the isolated perfused liver is useful for studying directly the functional level of the organ as drug metabolizing tissue.
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  • Yoshiaki NISHIJIMA, Yutaka SAKAI
    1975 Volume 25 Issue 3 Pages 335-344
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    An action of fentanyl, a short-acting narcotic, on the reflex discharge in the digastric nerve induced by the inferior alveolar nerve stimulation was investigated in α-chloralose anesthetized cats. In the ipsilateral digastric reflex discharge, there were an early phase induced by stimulus exciting Aα fibers and a late phase appearing when Aδ fibers were also stimulated. Following dorso-lateral cordotomy at the obex level, an isolation of the spinal trigeminal nucleus caudalis, a total area in the digastric reflex discharge decreased, while its first peak amplitude was little affected, indicating a disappearance of the late phase and a preservation of the early phase. Fentanyl depressed both the total discharge area and the first peak amplitude. After dorsolateral cordotomy, the depression of the area decreased considerably, whereas that of the amplitude decreased slightly. Results indicate that fentanyl depressed both the early phase which is activated by the Aα fiber stimulation, not via the subnucleus caudalis and the late phase which is activated by the Aδ fiber stimulation via the subnucleus caudalis or its surroundings. The latter action would be related to the analgesic action of fentanyl.
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  • Isao NEGISHI, Yoshio AIZAWA
    1975 Volume 25 Issue 3 Pages 345-348
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Masakatsu TAKAHASHI, Masao KOIDA, Hiroshi KANETO, Yutaka GOTO, Sumitak ...
    1975 Volume 25 Issue 3 Pages 348-349
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Norio HIMORI, Hiroshi ONO, Norio TAIRA
    1975 Volume 25 Issue 3 Pages 350-352
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • K.C. SINGHAL
    1975 Volume 25 Issue 3 Pages 352-354
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Fumiaki HATA, Tomohiro MATSUDA, Hiroshi YOSHIDA
    1975 Volume 25 Issue 3 Pages 354-357
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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