The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 25, Issue 2
Displaying 1-18 of 18 articles from this issue
  • Keiji NAKAMURA, Susumu MIZOGAMI, Kazuo NAKAMURA
    1975 Volume 25 Issue 2 Pages 85-92
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In unanesthetized and unrestraint rats, the administration of L-DOPA (20 mg/kg i.p.) with a peripheral decarboxylase inhibitor, Ro 4-4602 (50 mg/kg i.p.), markedly lowered blood pressure in DOCA-salt hypertensive rats (DHR) much more than it did in spontaneously hypertensive rats (SHR) or three types of normotensive controls; normal (NR), uninephrectomied and DOCA only. L-DOPA plus Ro 4-4602 did not change the renal hypertension induced by clipping a renal artery and uninephrectomy (RHR). The marked fall in blood pressure of DHR after L-DOPA plus Ro 4-4602 seemed to correlate with the accumulation of dopamine in the medullapons and hypothalamus, and of DOPA content in the medulla-pons. In RHR, accumulation of dopamine in the medulla-pons and hypothalamus was markedly lower than that in DHR, SHR and NR. Bilateral destruction of dopaminergic neurons in the striatum with 6-hydroxydopamine did not change blood pressure lowering activity of L-DOPA Plus Ro 4-4602 in NR and DHR. Spiroperidol (0.01 mg/kg i.p. × 2) caused no effect on the fall in blood pressure of DHR after L-DOPA plus Ro 4-4602, whereas the same doses of spiroperidol reduced amantadine-induced stereotyped behavior in DHR. These data suggest that the pronounced fall in blood pressure of DHR after L-DOPA plus Ro 4-4602 may be related to the marked accumulation of DA or DOPA in the brainstem, most probably in its noradrenergic neurons, but involvement of DA neurons per se may be minimal. Hypotensive reactivity of brainstem neurons with the DA accumulation is in the order of; DHR>SHR=NR>RHR.
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  • Keiji NAKAMURA, Kazuo NAKAMURA
    1975 Volume 25 Issue 2 Pages 93-100
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The intraventricular administration of α-adrenoceptive blocker (phentolamine) or dopamine (DA)-β-hydroxylase inhibitor (diethyldithiocarbamate) was found to abolish the most pronounced fall in blood pressure (BP) of freely moving DOCA-salt hypertensive rats (DHR) observed among normotensive or various types of other hypertensive rats after L-DOPA with combination of a peripheral decarboxylase inhibitor (Ro 4-4602). L-DOPA plus Ro 4-4602 markedly reduced the pressor response to electrical stimulation of the posterior hypothalamus, midbrain reticular formation and dorsal medulla oblongata in freely moving, unanesthetized or anesthetized DHR. L-DOPA plus Ro 4-4602 potentiated the depressor component in BP response to the posterior hypothalamic stimulation of the anesthetized DHR. These results suggest that L-DOPA plus Ro 4-4602 markedly lowers BP of DHR due to stimulation of α-adrenoceptor in the brainstem with effluxed noradrenaline after dopamine accumulation in the brainstem noradrenergic neurons and also at least partly due to blockade of the brainstem pressor areas.
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  • R. LISCIANI, G. DE FEO, V. CIOLI, S. PUTZOLU
    1975 Volume 25 Issue 2 Pages 101-107
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Bendazac has anti-inflammatory effects which are different from or complementary to those of corticosteroids; therefore, it has been associated with hydrocortisone or dexamethasone, in the attempt to obtain a dermatological preparation with a wide range of therapeutic applications. Results in laboratory animals were discouraging, in that a diminished activity was observed. On the other hand, bendacort or (pregn-4ene 3, 20 dione 11β, 17α, 21 trihydroxy, 21 ester with acetic acid [(1-phenylmethyl-1H-indazol-3-yl)-oxy], inhibited both types of inflammatory responses which are sensitive either to bendazac or corticosteroids. Moreover, in acetic acid-induced erythema, which is sensitive to both types of drugs, AF 2071 had stronger effects than those produced by bendazac or corticosteroids. Therapeutic and theoretical implications of these results are discussed.
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  • Akira KIMURA, Hiromi HAYASHI, Masaaki KURAMOTO
    1975 Volume 25 Issue 2 Pages 109-120
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Urchi-toxins (crude Urchi-toxin F2 and Urchi-toxins F3, F4 and F5) derived from Toxopneustes pileolus were investigated physicochemically and pharmacologically. F22 was found to be a mixture of several substances (F3, F4 and F5) being basic peptides or proteins. F2 and F3 inhibited strongly and slightly the cardiac movement of experimental animals, respectively, while F4 and F5 rather stimulated the heart beat. F2 and F3 elicited remarkable contraction of the small intestine. F2, F3 and F5 stimulated contraction of the uterus. Actions of F2 on smooth muscles were inactivated by chymotrypsin.
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  • Makoto OKA, Masanao SHIMIZU
    1975 Volume 25 Issue 2 Pages 121-127
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A simple avoidance procedure in mice was investigated for the purpose of testing psychotropic drugs. A box with two compartments, darkened and lightened, was used. Mice were put into the darkened compartment where they would be punished unless they moved into the lightened compartment within 5 sec. Most of mice quickly acquired an active avoidance in this apparatus with training less than 50 successive trials. Major tranquilizers such as chlorpromazine, haloperidol, clozapine and oxypertine depressed the avoidance response at doses lower than those at which the escape response was impaired. Diazepam and doxepin had depressant effects at doses which impaired the escape response. Imipramine and nortriptyline did not affect the avoidance response at the doses tested. It is concluded that mice quickly acquire an active avoidance under the present procedure and that this conditioned behavior is selectively depressed by major tranquilizers.
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  • Yoshikazu YAMATAKE, Hitoshi KATO, Keijiro TAKAGI
    1975 Volume 25 Issue 2 Pages 129-139
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Responses of the perfused forelimb paw small vein in anesthetized dog to vasoactive agents including serotonin, histamine, bradykinin, acetylcholine and epinephrine were investigated together with their modification by anti-inflammatory drugs. Venous perfusion with blood frequently caused venospasms which could not be attenuated by anesthetics, gallamine or phentolamine. In perfusion experiments both with blood and with Krebs-bicarbonate solution, close i.v. injections of epinephrine, serotonin and acetylcholine caused marked venoconstrictions (threshold doses in blood perfusion experiments, about 1, 3 and 300 ng, respectively), whereas bradykinin and histamine produced only weak constrictive responses even in large doses of more than 3 μg. Close i.v. injections of non-steroidal anti-inflammatory drugs, i.e. phenylbutazone, 150 μg/min, sodium salicylate, 500 μg/min, indomethacin, 50 μg/min, aminopyrine, 300 μg/min and benzydamine, 10 μg/min, nonspecifically depressed the venoconstrictor responses to epinephrine, serotonin, acetylcholine, bradykinin and histamine. A steroidal anti-inflammatory drug, hydrocortisone, however, tended to enhance the effect of epinephrine with no influence on the effects of the other vasoactive agents. The results suggest that the inhibitory effects of non-steroidal antiinflammatory drugs on the venoconstrictor responses to the vasoactive agents may contribute to their anti-inflammatory activity through the inhibition of facilitated vascular permeability due to the rise in hydrostatic pressure of the fine blood vessels.
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  • Noboru TODA, Hachiro USUI, Mieko KIMURA, Yoshinori ITOKAWA
    1975 Volume 25 Issue 2 Pages 141-149
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In isolated rabbit aortas, ventricles and left atria, the addition of Cd++ (0.5 mM) caused a decrease in the content of Ca++ and an increase in the Cd++ content. Contents of Mg++ and Zn++ were not significantly altered. Cysteine (1 mM) applied simultaneously with Cd++ prevented the Ca++-depleting action and also the accumulation of Cd++. Treatment of the tissues with Ca++-free media, EGTA (5 mM) and EDTA (5 mM) also reduced the content of Ca++. Treatment with Cd++ and EGTA did not significantly alter the extracellular space measured with 14C-inulin. The contractile response of aortic strips to noradrenaline and K+ was abolished by 0.5 mM Cd++. This inhibition was completely prevented by cysteine (1 mM) when noradrenaline was used as a stimulant, and partially prevented when K+ was used. Aortic contractions induced by noradrenaline and K+ were also attenuated by removal of Ca++ from bathing media and EGTA, the attenuation of the response to the ion being greater than that with the amine. Contractions of left atria driven electrically were abolished by 0.5 mM Cd++. Cysteine prevented only partially the inhibitory effect of Cd++. It may be concluded that Cd++ binds SH groups of membrane constituents to prevent influxes of Ca++, thus decreasing the content of Ca++ and reducing the reactivity of aortas and the contractility of atria.
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  • Yasusuke MASUDA, Ichiro YANO, Shigeo SUMIDA, Tadashi MURANO
    1975 Volume 25 Issue 2 Pages 151-160
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Direct action of CCl4 on rat liver plasma membranes and microsomes was investigated biochemically and morphologically in vitro. Plasma membranes or microsomes were pre-incubated with CCl4, then subjected to enzyme assays and electron microscopic observations. In plasma membranes, Mg++-ATPase lost its activity remarkably corresponding to the amount of CCl4, whereas (Na+-K+)-ATPase remained unaffected. 5'-nucleotidase and leucine aminopeptidase activities decreased to some extent but only with a large amount of CCl4. NADH-cytochrome c reductase activity also decreased, but not NADH-ferricyanide dehydrogenase activity. Some alterations of unit membrane structure and a complete disappearance of hexagonal patterns were observed electron microscopically in CCl4-pretreated plasma membranes. In microsomes, a marked loss of glucose-6-phosphatase activity was detected. NADH- and NADPH-cytochrome c reductase activities also decreased to some extent, whereas NADH-ferricyanide dehydrogenase activity remained unchanged. Some of these results show similar tendencies to those observed with the in vivo administration of CCl4. Thus, alterations of plasma membranes in vivo may indeed be partly due to a direct action of CCl4.
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  • Yasuo ENDO, Yasumi OGURA
    1975 Volume 25 Issue 2 Pages 161-169
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    N-Acetylhistamine-deacetylating activity was observed in all tissues tested of rats, mice and guinea-pigs. The liver, kidney, spleen and brain showed the high enzymatic activity. The major part of activity was localized in the cellular soluble fraction. In the brain, enzymatic activity was localized in a similar level in both the 100, 000 g supernatant and 10, 000 g sediment. The deacetylating activity was markedly increased by the addition of Mn++. Na+, K+, Li+, Ca++ and Mg++ had no effect. The Mn++ concentration optimum for the activity was in a range 0.5-1 mM. Co++ enhanced the activity at a low concentration and inhibited it at a high concentration. Cu++ Zn++, Hg++, Cd++ and p-chloromercuric benzoate (PCMB) inhibited the activity. The PCMB-inhibited activity was partially restored by the addition of glutathione-SH or cysteine. The optimum pH of the enzymatic reaction was 8.0 in the presence of Mn++. These properties were common among the enzymes in different tissues.
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  • Ikuko UENO
    1975 Volume 25 Issue 2 Pages 171-179
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    3H-luteoskyrin was injected subcutaneously into male and female mice and its radioactive compounds in the liver and excreta were analyzed. The radioactive compounds in the subcellular fractions of the liver could be extracted into ether under acidic conditions, and those in the excreta were recovered by extraction with ethanol. One of the radioactive compounds isolated from the liver and the feces was identified as unmetabolized 3H-luteoskyrin by thin-layer chromatography, gel filtration and spectrophotometry. In the liver subcellular fractions, mitochondria and cell debris contained 3H-luteoskyrin almost exclusively, while in the postmitochondrial fraction 3H-luteoskyrin corresponded to one half of the total radioactive compounds. The urine contained radioactive compounds other than 3H-luteoskyrin one of which was separated by the gel filtration. It was concluded that, after preferential distribution in the subcellular fractions, especially in the mitochondria and cell debris, of the liver, luteoskyrin is excreted as such in the feces and as a metabolite in the urine.
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  • Norio KURIHARA
    1975 Volume 25 Issue 2 Pages 181-187
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Anaphylaxis was induced in vitro in the small intestine, lung, aorta and heart of activity sensitized guinea pigs by adding the antigen after immersion in Tyrode solution, and released histamine and 5-HT were spectrophotofluorometrically determined to investigate the effect of corticosteroids on the releases. Dexamethasone administration markedly reduced the release of histamine and 5-HT in anaphylaxis, but DOCA exerted no effect on the release of these mediators from the tissues. On the other hand, aldosterone significantly decreased the release of histamine from the tissues in anaphylaxis, but did not produce any reduction in the release of 5-HT. The authors previously spectrophotofluorometrically determined the amount of mediators released from tissues of sensitized guinea pigs by addition of an antigen, and reported that while histamine was released on application of the antigen, 5-hydroxytryptamine (5-HT) was spontaneously released without antigen application (1). The purpose of the present experiment was to investigate the effect of corticosteroids on the release of the mediators from tissues of sensitized guinea pigs in anaphylaxis.
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  • Hiroshi KIMURA, Kinya KURIYAMA
    1975 Volume 25 Issue 2 Pages 189-195
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A simple and sensitive microradiometrical assay method for L-glutamic acid decarboxylase (GAD: EC 4.1.1.15) has been designed. Cerebral tissue was frozen and sectioned at 300 μ thickness, after which the slice was further dissected into rectangular blocks (750 750 μ). The GAD activity was assayed microradio-metrically. The incubation vessel held a volume of approximately 500 μl and the incubation mixture was 90 μl. The 14CO2 evolved from L-[l-14C]-glutamic acid was absorbed with a filter paper immersed in 100 μl of hyamine base. GAD activity in neuronal tissues containing less than 5-10 μg of protein was easily and accurately detected by this method. The assay was found to be linear at 5-500 μg of protein concentration in various CNS preparations. Utilizing this microradiometric assay method, it was found that in the rat hypothalamus, the distribution pattern of GAD activity was essentially the same as that of GABA.
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  • Osamu KANEKO
    1975 Volume 25 Issue 2 Pages 197-205
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Enzymic properties of diamine oxidase (DAO) and histaminase were compared. The enzymic activities of a partially purified preparation from hog kidney were determined by measuring oxygen consumption using cadaverine and histamine as substrates for DAO and histaminase, respectively. Differences were found in the effects of various reagents on the two activities. Although NH2OH inhibited to a similar extent the activities of DAO and histaminase, NaNO2, (NH4)2SO4 and C2H5OH affected the two activities differently. Moreover, NH2OH and NaNO2 had no effects on the pS curves of the two enzymes. (NH4)2SO4 and C2H5OH had no effect on the pS maximum of histaminase, but shifted the pS maximum to a higher concentration of cadaverine. Furthermore, marked differences in the mechanisms of action of DAO and histaminase were apparent from the effects of NH2OH, NaNO2, (NH4)2SO4 and C2H5OH on the two activities as measured from Lineweaver-Burk plots. These results indicate that the enzymic properties of DAO and histaminase are different and suggest that they are probably different enzymes.
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  • Jiro SUGIMOTO, Atsuko FURUMICHI
    1975 Volume 25 Issue 2 Pages 207-209
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Shoji MARUYAMA, Tadashi KAWASAKI
    1975 Volume 25 Issue 2 Pages 209-213
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Hidenori OHASHI, Tadashi TAKEWAKI, Nobuo SHIBATA
    1975 Volume 25 Issue 2 Pages 214-216
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Hiroshi Y. WATANABE, Hiroshi KUNO, Kazuo WATANABE
    1975 Volume 25 Issue 2 Pages 216-219
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Wen-Chang CHANG, Sei-itsu MUROTA, Susumu TSURUFUJI
    1975 Volume 25 Issue 2 Pages 219-221
    Published: 1975
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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