The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 24, Issue 2
Displaying 1-23 of 23 articles from this issue
  • Seiichi NURIMOTO, Nobuya OGAWA, Showa UEKI
    1974 Volume 24 Issue 2 Pages 175-184
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In order to clarify the neural mechanisms underlying the hyperemotionality induced by bilateral olfactory bulb ablations in rats, changes in emotional behavior were measured after various parts of the secondary olfactory structures had been lesioned and olfactory bulb ablations had been carried out. When the anterior olfactory nuclei, lateral olfactory tracts and prepiriform cortices were bilaterally lesioned simultaneously with olfactory bulb ablations, many rats died from lack of food intake, while on the contrary, the rats with bilateral lesions in the olfactory tubercle, anterior olfactory nuclei and olfactory bulb developed marked hyperemotionality immediately after the lesioning. Hyperemotionality of the latter rats included not only hyperreactivity similar to that observed in the septal rat but also a muricide of 90% in incidence, which is similar to rats with olfactory bulb ablations. From these results, it can be concluded that changes in the activity of the olfactory tubercle were the most important for the development of hyperemotionality following bilateral ablations of the olfactory bulb in the rat.
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  • Seiichi NURIMOTO, Nobuya OGAWA, Showa UEKI
    1974 Volume 24 Issue 2 Pages 185-193
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of psychotropic drugs on hyperemotionality of the rat with lesions in the olfactory system, including the olfactory bulbs and olfactory tubercles (O.B.-O.T. rat), were investigated, and compared with the neurotoxic effects of these drugs measured on rotarod performance of the mice with bilateral olfactory bulb ablations (O.B. mice). Chlorpromazine, reserpine and meprobamate inhibited the hyperemotionality at doses close to their neurotoxic dose. Pentobarbital showed only a slight effect on the hyperemotionality at subhypnotic doses. Chlordiazepoxide, diazepam and haloperidol markedly inhibited the hyperemotionality at lower doses without causing neurotoxicity. Imipramine and arnitriptyline selectively inhibited mouse-killing behavior (muricide) of the O.B.-O.T. rat without affecting the other hyperemotional responses to various stimuli, thus differing from tranquilizers. The mode of action of these drugs in the O.B.-O.T. rat was essentially the same as observed in either the O.B. and the septal rats. For evaluating the effects of psychotropic drugs, the O.B.-O.T. rats are superior to the O.B. and septal rats, as they share both offensive aggression of the O.B. rat and hyperreactivity of the septal rat, and furthermore they exhibited muricide in a much higher incidence soon after the brain lesions.
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  • Tetsuya KAMATAKI, Haruo KITAGAWA
    1974 Volume 24 Issue 2 Pages 195-203
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of lyophilization and storage of rat liver 9, 000×g supernatant fraction or microsomes on activity of aniline hydroxylase, contents of cyt. P-450 and cyt. b5 and aniline-induced P-450 difference spectrum were studied. The lyophilization of rat liver 9, 000×g supernatant fraction or microsomes produced about 20% decrease in the activity of aniline hydroxylase. Aniline hydroxylase was stably stored for 6 months if lyophilized 9, 000×g supernatant fraction of rat liver had been stored in an atmosphere of nitrogen or in a low pressure of air. Activity of aniline hydroxylase and contents of cyt. P-450 and cyt. b5 were not reduced during aerobical storage for a week. When lyophilized microsomes were stored for 6 months anaerobically, aniline hydroxylase, cyt. P-450 and cyt. b5 were more stable as compared to aerobical storage. However, activity of aniline hydroxylase was reduced approx. 40% by the storage. The reduction of aniline hydroxylase activity was more significant than that of contents of cyt. P-450 and cyt. b5. Reduction of either activity of aniline hydroxylase or contents of cyt. P-450 and cyt. b5 was more marked when lyophilized microsomes were stored with glycerol. Aniline hydroxylase in lyophilized 9, 000×g supernatant fraction from phenobarbital treated rabbit was stably stored, and aerobically little activity was lost during storage for 7 months.
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  • Yasuyuki NOMURA, Hiroshi TAKAGI
    1974 Volume 24 Issue 2 Pages 205-212
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Electrophoretic mobility of rabbit blood platelets was measured by cell electrophoresis and by this method electrochemical properties of platelets and 5hydroxytryptamine (5HT)-platelets or various 5HT releasers-platelets interactions were examined. It was found that the mobility of platelets was -0.98 μ/sec/volt/cm in 0.02 M Tris saline (pH 7.5). Decreases in the mobility of platelets by treatment with neuraminidase or trypsin were observed at 40% and 20% respectively and sialic acid was released by both treatments. The pattern of cation charge-reversal spectra of platelets was similar to the carboxyl and phosphate groups in spectra of Bungenberg de Jong. Addition of 5HT, lipopolysaccharide (LPS) and heparin did not influence the mobility of platelets in the neutral pH region. Under the conditions producing release of 5HT from platelets, the treatments with the plasma 5HT releasing factor, thrombin, LPS or chlorpromazine decreased the mobility of platelets, while that with reserpine, tyramine or imipramine did not. These findings suggest that carboxyl group of sialic acid is responsible for the negative charge of platelets surface but it may not interact with 5HT and that the membrane is one of the sites of 5HT releasing actions of the plasma factor, thrombin, LPS or chlorpromazine.
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  • 1. INHIBITION OF ION ACCUMULATION BY ETHACRYNIC ACID AND FUROSEMIDE
    Munekazu GEMBA
    1974 Volume 24 Issue 2 Pages 213-218
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Rat kidney cortex mitochondria accumulated calcium remarkably in the absence of phosphate in the medium. ATP-dependent calcium and magnesium accumulation in rat kidney cortex mitochondria were inhibited by ethacrynic acid and furosemide, and the potassium accumulation stimulated by valinomycin was also inhibited by both diuretics. Oxygen consumption of kidney cortex mitochondria, on the other hand, was depressed by ethacrynic acid, but not at all by furosemide. Studies of this report place major emphasis upon the relationship between the effects of both diuretics on ion accumulation and on electron transport system.
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  • Tsutomu URUNO, Issei TAKAYANAGI, Kazuhiko KUBOTA, Keijiro TAKAGI
    1974 Volume 24 Issue 2 Pages 219-226
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Inhibitory responses of the isolated rat uterus to papaverine, Aspaminol and isoprenaline were potentiated by aminophylline that inhibits phosphodiesterase. The inhibitory responses to papaverine and isoprenaline were decreased by imidazole that stimulates phosphodicsterase activity, while the inhibitory response to Aspaminol was little influenced by imidazole. Papavcrine strongly inhibited phosphodiesterase from the rat uterus, but Aspaminol did not influence phosphodiesterase activity. These results indicate that papaverine and isoprenaline are mediated through an increase of the intracellular level of cyclic AMP and also indicate that the inhibitory response of the rat uterus to Aspaminol is not concerned with the amount of intracellular cyclic AMP increased by inhibiting phosphodiesterase. Further, the results support the theory that there are two mechanisms for the so-called papaverine-like antispasmodics.
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  • Katsunori OGURO, Koroku HASHIMOTO
    1974 Volume 24 Issue 2 Pages 227-233
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of various coronary vasodilators on the coronary, the femoral and the renal circulations were compared with those of nitroglycerin, and classified on the basis of differences in the mode of action. Coronary vasodilators used in this study, caused a significant increase in the rate of both the coronary and the femoral blood flows while a slight increase or even a decrease in the rate of the renal blood flow was observed. The coronary vasodilating activity was in the following order; nifedipine>nitroglycerin>iproveratril>dipyridamole, prenylamine, lidoflazine, papaverine>carbochromene, trapymin>khellin, which was approx. equivalent to 1: 1/3: 1/10: 1/100: 1/300: 1/3000. The order of effectiveness of vasodilation in the coronary circulation produced by these compounds was similar to that observed in femoral circulation. Lidoflazine, dipyridamole, prenylamine, carbochromene and khellin, however, caused a dose-dependent vasoconstriction in renal circulation. A large dose of papaverine caused a diphasic response in the renal circulation. From these experimental results, lidoflazine, dipyridamole, carbochromene and khelline can be classified as “specific coronary vasodilators”, while nifedipine, nitroglycerin, iproveratril and trapymin are “non-specific coronary vasodilators”. Papaverine and prenylamine do not appear to belong to these two categories.
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  • Heitaroh IWATA, Hiroshi OKAMOTO, Ikuko KURAMOTO
    1974 Volume 24 Issue 2 Pages 235-240
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The influence of lithium administration on brain serotonin metabolism and the serum tryptophan level in rats was investigated. The brain tryptophan, serotonin and 5-hydroxyindole acetic acid contents did not change after a single injection of lithium, but did increase significantly after repeated injections. A single injection of lithium caused a marked decrease in the serum total tryptophan level, but did not change the ratio of free to albumin bound tryptophan. On the contrary, repeated injections of lithium caused a significant increase in serum total tryptophan, and decrease in the ratio of free to bound tryptophan. Addition of lithium ion to normal rat serum in vitro did not change the ratio of free to bound tryptophan. A single injection of lithium produced a marked rise in serum nonesterified fatty acid, which is known to affect the binding of tryptophan by albumin.
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  • Sadao NAKANE, Takeshi SAKAI
    1974 Volume 24 Issue 2 Pages 241-246
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of biogenic monoamines and their precursors on stress ulcers and secretion in stomach were investigated herein. Norepinephrine, 5-HT and their precursors prevented formation of stress ulcer at any level of endogenous monoamines in reserpine or iproniazid-treated rats. These same agents did not affect the stressinduced decrease in the output of PSB but increased the pH value of gastric juice.
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  • Yasumitsu YAMANAKA, Shizuko KONO
    1974 Volume 24 Issue 2 Pages 247-252
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Mice were made alcoholic on an alcohol liquid diet. The rate of serotonin synthesis in the brains of chronically alcoholic mice was found to be almost half that of the control group. However, the effect of acute alcoholism demonstrated a tendency to increase the rate of serotonin synthesis. Brain levels of 5HIAA were decreased during chronic alcohol ingestion, however, the brain levels of serotonin in alcoholic mice were similar to those in the untreated mice. These data suggest that serotonergic units in the central nervous system are inhibited during chronic alcoholism.
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  • Junnosuke YAMAMOTO, Atsushi SEKIYA
    1974 Volume 24 Issue 2 Pages 253-259
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Propranolol produces a sustained rise in blood pressure in the rat, but little change in the guinea pig. In order to elucidate this distinct difference, the following experiments were carried out: (a) The pressor effect of propranolol was studied while the vascular tone was changed by infusion of several vasoactive substances in the guinea pig; (b) The effect of propranolol on the isolated atria of rats and guinea pigs was also compared. Propranolol always produced a pressor action during the infusion of adrenergic β-stimulating agents, but not during vasopressin infusion. In spontaneously beating or electrically driven guinea pig atria, propranolol reduced the contractile force to a greater extent than in rat atria. It is concluded that the difference in action of propranolol on the blood pressure of rat and guinea pig may be explained by the following two reasons: (a) the β-adrenoceptive vasodilator tone in skeletal muscle is stronger in the rat than in the guinea pig; (b) the heart of the rat is less sensitive to propranolol than that of the guinea pig.
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  • Hitoshi KATO, Yuji NOGUCHI, Kenichiro NAKAO, Keijiro TAKAGI
    1974 Volume 24 Issue 2 Pages 261-270
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The cardiovascular beta-adrenergic receptor blocking activities of YB-2 and its optical isomers were investigated in isolated guinea pig atria and anesthetized dogs, and compared with that of propranolol. In isolated guinea pig atria, the positive inotropic and chronotropic responses to isoproterenol were competitively antagonized by these agents, and the order of beta-adrenergic blockade was as follows: 1YB-2>dl-YB-2 ?? propranolol>d-YB-2. In anesthetized dogs, the effects of isoproterenol and cardiac sympathetic nerve stimulations on diastolic blood pressure, heart rate and dLVP/dt were competitively antagonized by the beta-adrenergic blocking agents. The blockade appears to be specific for beta-adrenergic receptors. In these experiments, cardioselectise blocking activity was not observed with any agent employed. 1-YB-2 was 1.7-2 times more potent than dl-YB-2 and 50-100 times more potent than d-YB-2 in antagonism against the cardiovascular responses to isoproterenol and nerve stimulations. dl-YB-2 was 1.2-1.7 times more potent than propranolol. The results coincided with those in isolated guinea pig atria. In conclusion, YB-2 and its optical isomers appear to have a similar potency ratio for the blockade of cardiac beta-adrenergic receptor stimulations as is the case with propranolol.
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  • II. MODE OF ACTION OF ETHACRYNIC ACID ON MITOCHONDRIAL CALCIUM PUMP
    Munekazu GEMBA
    1974 Volume 24 Issue 2 Pages 271-277
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of ethacrynic acid on mitochondrial Ca2+-accumulation were examined in the rat kidney. The inhibitory effect of the drug on Ca2+-accumulation was reversed by cysteine or gluthathione. The addition of phosphate to the medium abolished the inhibitory effect of ethacrvnic acid on Ca2+-accumulation of kidney cortex mitochondria. On the other hand, acetate enhanced that of the drug. The inhibition of Ca2+-accumulation by mersalyl was reversed by cysteine, but was not by phosphate, differing from ethacrynic acid. Ethacrynic acid inhibited the activity of mitochondrial ATPase observed in the presence of CaCl2, but not the enzyme activity in the presence of MgCl2. The main inhibitory effect of ethacrynic acid on mitochondrial Cat2+-accumulation may be due to an action on mitochondrial ATPase.
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  • Tomohiko KIMURA, Masaru KOKUBUN, Koroku HASHIMOTO
    1974 Volume 24 Issue 2 Pages 279-283
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Chronotropic and inotropic effects of glucagon were compared with those of norepinephrine using the excised SA node and the papillary muscle preparations cross-circulated with a donor dog. Glucagon was administered i.v. to the donor dog at doses of 1 to 30 μg/kg, which caused a marked chronotropic but less marked inotropic effect. Cardiohemodynamic response to glucagon of anesthetized dogs was simulated by an acceleration induced by atrial pacing. It was concluded that glucagon is more effective on chronotropism than on inotropism, and that its cardiohemodynamic effects are mainly ascribed to the increased heart rate.
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  • Yoshihide YAMASAKI, Kinya KURIYAMA
    1974 Volume 24 Issue 2 Pages 285-290
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of acute ethanol administration on the axoplasmic flow in retinal ganglion cells of rats were studied by intraocular injection of 3H-1-leucine. Ethanol induced a facilitation of the fast axoplasmic flow without affecting the slow axoplasmic flow. Pretreatment with colchicine almost completely eliminated the fast flow in both control and ethanol-treated rats, while cycloheximide did not significantly affect the facilitation of the fast flow induced by ethanol. The extent of ethanol-induced changes in the fast flow did not directly correlate with the level of ethanol or acetaldehyde in the blood. Neither adrenalectomy nor hypophysectomy modified significantly the facilitation of the fast axoplasmic flow due to ethanol administration. Present results indicate that ethanol-induced facilitation of the fast axoplasmic flow is not due to the direct effect of ethanol or acetaldehyde or to changes in pituitaryadrenal function.
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  • Masaru KUNITOMO, Toshiyuki NAGAKURA
    1974 Volume 24 Issue 2 Pages 291-298
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of 1-[2-(dodecyloxy)ethyl]pyrrolidine hydrochloride (DEP) on Ascaris muscle cells were investigated using electrophysiological techniques. The average resting potential of the muscle cells was 33.7±0.26 mV (S.E.M.). DEP caused depolarization and decreased spike frequency in single muscle cell. This DEP-induced depolarization was not antagonized by d-tubocurarine, other cholinolytics and tetrodotoxin. DEP reduced the membrane potential of the muscle cells bathed for 2 hr in the calcium-free solution containing EGTA but did not produce a contraction. In the presence of lecithin or cephalin in the medium, DEP did not cause depolarization, which suggests that DEP could produce a depolarization by changing the conformation of membrane lipoprotein and then by increasing the ion permeability. It is demonstrated that some divalent cations other than calcium ion could activate the contractile system of Ascaris muscle.
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  • Takashi NOSE, Tomio SEGAWA
    1974 Volume 24 Issue 2 Pages 299-305
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The inhibitory effect of certain centrally acting drugs, including antiparkinsonian agents, tricyclic antidepressant and phenothiazine, was studied in vitro on the accumulation of dopamine into a crude mitochondrial fraction (P2-fraction) from rat striatal homogenate, and the site of inhibition was studied by further fractionating the P2-fraction into synaptic vesicles fraction (P2V-fraction) and supernatant fluid (P2S-fraction). Many antiparkinsonian agents, such as benztropine, trihexyphenidyl, ethopropazine, diphenhydramine or 6, 6, 9-trimethyl-9-azabicyclo[3, 3, 1] non-3β-y1 α, α-di(2-thienyl) glycolate hydrochloride monohydrate (PG-501), inhibited dopamine accumulation into P2-fraction from rat striatal homogenate in concentrations of 10-5-10-4 M, though atropine did not inhibit the amine accumulation even in a concentration of 10-4 M. Furthermore, benztropine, one of the most potent inhibitors of dopamine accumulation into P2-fraction, inhibited the accumulation into P2V-fraction to a greater extent than that into P2S-fraction and PG-501 inhibited the accumulation into P2S-fraction to a greater extent than that into P2V-fraction. The possible site of action of these two agents is discussed herein.
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  • Takao KUBO, Yoshimi MISU
    1974 Volume 24 Issue 2 Pages 307-318
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Interactions between action of guanethidine (4 ×10-6 to 4×10-5) and Ca, Na or K were investigated in isolated hearts of rabbits. Positive chronotropic responses to electrical sympathetic stimulation and noradrenaline (NA) released by nicotine or high KCI were measured. Inhibitory drug action on responses was irreversible and reduced by raising Ca to 12.5 mM together with drug addition. The action was not reduced after the drug had been washed out and the Ca level was raised to 50 mM, after which it returned to normal. It was accelerated by lowering Na to 86 mM simultaneously, but not delayed by raising Na to 286 mM. After the drug was washed out with normal solution, NA released by 100 and 300 mM KCl was reduced to almost the same extent. When stimulation was done during washing with low Na solution, inhibitory drug action on responses and NA released by nicotine was reduced. It was not reduced, however, when nicotine was applied in normal Na solution after washing with low Na solution. During washing with high Na solution, it was accentuated, despite no modification by washing with isoosmotic sucrose or Li solution. Low or high Na solution alone did not modify the parameters. During washing with low K solution (3.5 mM), it was not modified. The hypothesis is presented that guanethidine increases permeability of nerve ending membrane to Na, thereby leading to adrenergic neuron blockade.
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  • Tomio SEGAWA, Masumi NAKANO
    1974 Volume 24 Issue 2 Pages 319-324
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Five days administration of Li (Li2CO3 2.5 mEq/kg, i.p. twice daily for 4 days, followed by one injection on the 5th day) to rats did not significantly alter brain serotonin (5-HT) levels. Animals appeared somewhat sedated but showed considerable exploratory and rearing behavior in new circumstances. Turnover rate of brain 5-HT as measured from the accumulation after inhibiting monoamine oxidase was decreased by repeated administration of Li. Furthermore, Li lessened the depletion rate of brain 5-HT by reserpine. These results suggest that certain of the effects of Li on manic states can be attributed to the reduced functional activity of brain 5-HT neurons.
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  • Issei MATSUBARA, Yoshito NAKAGAWA, Shoichi IMAI
    1974 Volume 24 Issue 2 Pages 325-326
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Yukisato ISHIDA, Norimoto URAKAWA
    1974 Volume 24 Issue 2 Pages 327-330
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Jiro SUGIMOTO, Mitsuhiko MURAKAMI
    1974 Volume 24 Issue 2 Pages 330-332
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Yoshimi MISU, Takao KUBO
    1974 Volume 24 Issue 2 Pages 332-334
    Published: 1974
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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