The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 28, Issue 3
Displaying 1-22 of 22 articles from this issue
  • Che-Hui KUO, Seiji ICHIDA, Fumiaki HATA, Hiroshi YOSHIDA
    1978 Volume 28 Issue 3 Pages 339-343
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The influences of synaptic plasma membranes on release of acetylcholine (ACh) from synaptic vesicles isolated from rat brain were examined. In the presence of ATP, Mg++ and Ca++ but absence of cytoplasm from the nerve endings, the synaptic plasma membranes did not increase ACh release indicating absence of a stimulating factor which is known to be present in the cytoplasm. In presence of ATP, Mg++ Ca++ and the cytoplasm, the synaptic plasma membranes inhibited ACh release from the synaptic vesicles in high K+ medium, though not in high Na+ medium. Binding of Ca++ by the synaptic plasma membranes was dependent on ATP, inhibited by Na+ and stimulated by K+. Thus, the synaptic plasma membranes may inhibit ACh release in high K+ medium due to reduction in the concentration of free Ca++.
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  • Nobuyoshi IWATA, Yutaka SAKAI
    1978 Volume 28 Issue 3 Pages 345-357
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In order to determine the cholinoceptive mechanism associated with cutaneous inhibition of jaw-closing and lumbar motoneurons, the area related to the inhibition produced by stimulation of the superficial radial nerve was identified by a lesion within the pontomedullary reticular formation and effects of drugs upon neurons were studied within this area. The cutaneous inhibition, as tested by the inhibition of monosynaptic reflex activity of jaw-closing and that of hindlimb spinal motoneurons was completely abolished by lesion of the medial portion of the pontomedullary reticular formation, but was little affected by lesions of the lateral portion. Intravenously administered physostigmine (0.15-0.30 mg/kg) excited 11 of 21 neurons whereas electrophoretic ACh (90 nA) excited 26 and inhibited 4 of 96 brainstem neurons located in this area. Eight of 11 physostigmine, and 4 of 26 ACh excited neurons were reticulospinal neurons with axonal conduction velocities of 20-40 m/sec. From results presented here together with those reported previously, these physostigmine sensitive and ACh excited brainstem neurons, reticulospinal and non-reticulospinal neurons, could be cholinoceptive interneurons of the polysynaptic inhibitory pathway, from the superficial radial nerve to jaw-closing and hindlimb spinal motoneurons.
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  • Masahiro YOSHIMURA, Shozo TAKAMURA, Tamako ISHIKAWA, Junko YOSHIDA, Ku ...
    1978 Volume 28 Issue 3 Pages 359-366
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In the presence of tripropylsulfonium bromide (TPS) (1×10-4 g/ml), a new compound, the phasic contraction of the isolated guinea pig ileum to 5-hydroxytryptamine (5-HT) (5×10-7 g/ml) was consistently enhanced (“TPS effect”). TPS alone increased moderately the spontaneous movement of the ileum. When the contraction height was calculated as the percentage of that to 5-HT alone, such was observed in the “TPS effect” to be 167.1±3.6% (mean±S.E., n=80). TPS did not enhance the contraction due to acetylcholine or histamine. The “TPS effect” remained unaffected in the presence of dibenzyline (1×10-7 g/ml), was abolished by morphine (1×10-6 g/ml), tetrodotoxin (2×10-8 g/ml) adenosine (3×10-6 g/ml) and atropine (1×10-7 g/ml) and was not observed under anoxic conditions. Eserine (1×10-8 g/ml) strengthened the “TPS effect” markedly. It is concluded that this effect may be the result of the potentiating effect of TPS on the action of 5-HT through the M receptors, possibly by the facilitation of the acetylcholine-liberation from the nervous tissue.
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  • Yoshio OHMIYA, Kengo NAKAI
    1978 Volume 28 Issue 3 Pages 367-373
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The uptake of benzyl alcohol by human erythrocytes and its binding to cell membranes were examined in vitro in relation to its hemolytic actions. The hemolysis induced by benzyl alcohol was found to be time-, dose- and temperaturedependent. Little or no hemolysis was observed until the concentration of benzyl alcohol increased over a certain level. Radiotracer studies revealed that in contrast to the rapid cellular uptake which was independent of temperature, the binding of benzyl alcohol to membranes increased gradually with time and was dependent mainly on the temperature. The critical hemolytic levels of the alcohol bound to membranes were estimated to be about 500 nmoles/mg protein. The results obtained herein suggest that the process of hemolysis induced by benzyl alcohol depends on the binding of the alcohol to erythrocyte membranes.
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  • Iwao YAMAMOTO, Naomasa MIKI, Shigeru KONDO, Shiro KAKIUCHI
    1978 Volume 28 Issue 3 Pages 375-381
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Accumulation of cyclic AMP was studied in guinea pig cerebral slices when Na+ levels in the bathing medium were varied or agents which affect tissue Na+ content were added. When NaCl was gradually replaced with Tris-HCl or choline chloride, cyclic AMP formation was progressively enhanced. When Na+ was below 30 mM, cyclic AMP formation reached the maximum (approximately 30 fold), but this increment was not blocked by tetrodotoxin. The stimulatory effect of high K+ was nearly linear over 120 mM and became much more prominent when Na+ was decreased to 30-40 mM in the bathing medium. The effect of high K+ also was not blocked by tetrodotoxin. Ouabain (10-4 M), electrical pulses and glutamate (5×10-3 M), each stimulated cyclic AMP formation about 17-, 7- and 5-fold, respectively. Tetrodotoxin (2×10-6 M) completely blocked the effects of electrical pulses and partially blocked the effects of glutamate and ouabain. It is suggested that the increase of cyclic AMP in cerebral cortical slices may be related to the decrease in Na+ gradient across the cell membrane.
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  • Saizo YANAURA, Shigeru ISHIKAWA
    1978 Volume 28 Issue 3 Pages 383-389
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Choleretic effects and properties of ursodeoxycholic and chenodeoxycholic acids given orally were investigated in comparison with dehydrocholic acid in conscious dogs with cholecystectomy. Ursodeoxycholic acid as well as chenodeoxycholic acid increased the bile flow and the concentrations of phospholipid, cholesterol and bile acids in the bile. After administration of either ursodeoxycholic acid or chenodeoxycholic acid, a great amount of each bile acid appeared in the bile. Ursodeoxycholic and chenodeoxycholic acids increased the outputs of phospholipid, cholesterol and bilirubin in the bile. On the other hand, dehydrocholic acid markedly decreased the concentrations and outputs of all the above materials in the bile, despite a considerable increase in the bile flow. After administration of dehydrocholic acid, 3α, 7α-dihydroxy-12-keto-cholanoic acid appeared in the bile instead of dehydrocholic acid. The results suggest that ursodeoxycholic and chenodeoxycholic acids are transported into the bile from the hepatic cells where they produce a choleresis due to the bile acid-dependent mechanism. Dehydrocholic acid is metabolized in the liver and the metabolites produce hydrocholeresis.
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  • Yoshikazu YAMATAKE, Saizo YANAURA
    1978 Volume 28 Issue 3 Pages 391-402
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    We devised a new method for measuring responses of canine airway musculature, bronchosecretion and bronchial vasculature simultaneously, in situ, and investigated the effects of prostaglandins F and E2 and antigen-antibody reaction by using this model. The right bronchial artery was perfused with blood at a constant flow under artificial respiration. Airway musculature response was measured as a change in ventilation overflow with a modification of the Konzett-Rössler method; the airway secretory activity was measured with our stopper method for secretion volume and with the glass plate method for viscosity. Close intraarterial injections of prostaglandin (PG) F, 0.01-10 μg, into the right bronchial artery produced bronchomuscular and vascular constrictions, while those of PGE2, 0.01-3 μg, produced dilatation in a dose dependent manner. A close intraarterial injection of 1 mg protein of ascaris suum antigen to dogs with positive skin reaction produced bronchoconstriction and vascular dilatation. Thirty min intraarterial infusions of PGF, 0.3-3 μg/min, and ascaris antigen, 0.03-0.3 mg protein/min, resulted in a dose-dependent increase in the volume of airway secretions, while those of PGE2, 0.1-1.0 μg/min, did not alter the secretory activity. These findings indicate that prostaglandin F in relatively high doses increases both bronchomotor tone and bronchosecretory activity, as does antigen-antibody reaction with ascaris antigen, and that the present method is useful for evaluating effects of drugs on the respiratory tract.
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  • Tadashi MURANO, Hiromi SENDA, Hiroyuki YAMAMOTO, Ichiro YANO
    1978 Volume 28 Issue 3 Pages 403-412
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Influence of morphine on the fine structure of mitochondria in the cell of zona fasciculata of adrenal cortex in mice treated chronically with morphine pellets was studied using the electron microscope. The transformation of mitochondrial structure was observed 12 hours after morphine pellet implantation and the degree of transformation reached a maximum at 48 hours. These changes, however, disappeared within 4 days. On the 4th day after implantation, removal of the pellet or levallorphan challenge resulted in alteration of the mitochondria with evidence of withdrawal syndrome. Reinjection of morphine to the mice immediately after removal of the pellet, however, prevented the appearance of such mitochondrial transformation. Chlorpromazine or sodium pentobarbital did not affect on the transformation of mitochondria.
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  • Takushi X. WATANABE, Kumiko SHIONO, Ken SAITO, Hirofumi SOKABE
    1978 Volume 28 Issue 3 Pages 413-422
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    3-Hydrazino-6-[N, N-bis (2-hydroxyethyl)amino]-pyridazine (L 6150) has been reported as an antihypertensive vasodilator drug. We determined antihypertensive effect of L 6150 for 11 weeks in spontaneously hypertensive (SHR) rats, deoxycorticosterone and salt (DOC) hypertension, and renal hypertension due to clipping (CLIP). The effects of hydralazine (HZ) and ecarazine (EZ) were also determined for comparison. L 6150, HZ, and EZ showed antihypertensive effects in SHR, DOC and CLIP hypertensive rats. These drugs increased heart rate in SHR and DOC rats. In CLIP hypertension heart rate tended to be higher for 9-10 weeks after the treatments. These treatments diminished incidence of the vascular disease in DOC and CLIP. We also determined renal effects of L 6150, HZ and EZ in normal rats. These drugs decreased urine volume, and excretion of osmotically active solutes, Cl, Na, and K for 180 min after bicarbonate saline load. It is concluded that L 6150 is an antihypertensive drug with characteristics of the vasodilator in rats.
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  • Hirokazu KITOH, Nobuo TOSHIOKA
    1978 Volume 28 Issue 3 Pages 423-431
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of repeated doses of tiopronin [N-(2-mercaptopropionyl)glycine] on elimination of 203Hg were determined by means of whole body counting after intravenous injection of 203Hg-methylmercuric chloride (Me 203HgCl), phenylmercuric acetate (Ph 203HgAc) or mercuric chloride (203HgCl2) into mice. The tissue distribution of 203Hg-mercury compounds was also observed, using a autoradiographic technique, and the effects of tiopronin were compared with those of 2, 3-dimercaptopropanol (BAL). Subcutaneous administrations of tiopronin stimulated excretion of radioelements from the whole body of mice given Me 203HgCl, the biological half-life of Me 203HgCl being shortened from 6.5 to 2.9 days. Autoradiographic studies showed that the radioactivities after Me 203HgCl injection were less in all organs in the tiopronintreated mice than in the controls after a temporary rise of radioactivities in the blood and secretory glands. The excretion of 203Hg from the mice given Ph 203HgAc or 203HgCl2 was also stimulated by tiopronin treatment, but the stimulation was much less than when the mice had been given Me 203HgCl. Repeated administrations of BAL remarkably increased the excretion of radioelement in the mice given Ph 203HgAc or 203HgCl2 but not Me 203HgCl. However, autoradiograms demonstrated that BAL enhanced accumulation of these compounds in the nervous system and muscle compared tic ith the control after injection of three different types of mercury compounds.
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  • Kazuhiro GOTO, Masao HISADOME, Yutaka MARUYAMA, Hiroshi IMAMURA
    1978 Volume 28 Issue 3 Pages 433-446
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    2-{4-(2-Imidazo[1, 2-a]pyridyl)phenyl}propionic acid (Y-9213) with analgesic, antipyretic and anti-inflammatory activities significantly inhibited hemolysis of rat erythrocytes. Activity of Y-9213 (100-500 μM) on hemolysis was more potent than that of phenylbutazone, and less potent than that of indomethacin. The spontaneous release of enzymes from rat liver lysosomes by incubation alone was significantly inhibited by Y-9213 (1-100 μM) to the same degree as phenylbutazone or tinoridine hydrochloride. Release of enzymes from the lysosomes by addition of phospholipase C (PLC, 0.03 units/ml) was slightly inhibited by Y-9213 (10-100 μM) and phenylbutazone (100 μM). Dexamethasone, prednisolone, hydrocortisone and tinoridine hydrochloride (1-10 μM) inhibited more potently the PLC-induced release than the spontaneous release. Y-9213 (1-100 μM) inhibited considerably the release of enzymes from intact lysosomes of rabbit polymorphonuclear (PMN) leukocytes. The release of enzymes from the PMN leukocyte lysosomes preincubated at 37°C for 15 min was strongly inhibited by dexamethasone, prednisolone and hydrocortisone (1-100 μM), but not by Y-9213, phenylbutazone and indomethacin (100 μM). Y-9213 (0.1-10 μM) also inhibited significantly the phagocytic secretion of lysosomal enzymes from PMN leukocytes without affecting phagocytosis of the particles. Activity of this agent was similar to that of phenylbutazone, and less active than that of indomethacin, dexamethasone or prednisolone. Our results suggest that Y-9213 may stabilize membranes of erythrocytes and lysosomes and inhibit phagocytic secretion of lysosomal constituents from PMN leukocytes.
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  • Saizo YANAURA, Tomokazu HOSOKAWA, Harumi KITAGAWA, Yoshikazu YAMATAKE
    1978 Volume 28 Issue 3 Pages 447-455
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    We devised a canine blood-perfusion preparation which made feasible administration of drugs directly at the local tracheal site. The hypothesis of Salem and Aviado on cough mechanism that a local airway constriction induced by stimuli may be a trigger in stimulating cough receptors was investigated using this preparation. Close intraarterial injections of acetylcholine (ACh) and histamine did not elicit a cough although intense tracheal constrictions were evident. The cough reflex elicited by electrical stimulation of the mucosa of isolated upper trachea in situ was accompanied by a slight systemic hypotension, tracheal vasodilatation and tracheal muscular constriction. The latter two changes occurred after a time lag following coughs. Close intraarterial infusions of isoproterenol and papaverine caused a prominent tracheal dilatation, but did not suppress the coughs. Pretreatment with atropine sufficiently inhibited cholinergic tracheoconstriction but had no effect on the electrically induced coughs. Furthermore, an augmentation of the tracheal muscular tone produced by an infusion of ACh did not enhance the cough reflex. In light of our observations, the aforementioned hypothesis should be reconsidered.
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  • Hideyuki TAKENAGA, Tetsuo MAGARIBUCHI, Hiromichi NAKAJIMA
    1978 Volume 28 Issue 3 Pages 457-464
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of diltiazem were investigated on the isolated portal vein of the guinea pig in hypertonic solution. Hyperosmolarity was produced by sucrose. In contrast to a small and somewhat irregular spontaneous contraction in isotonic solution, the portal vein in hypertonic solution elicited a spontaneous contraction at regular intervals and with a large amplitude and low frequency. The spontaneous phasic contraction in hypertonic solution was not affected by tetrodotoxin, atropine and propranolol. Phentolamine also had no significant influence in some preparations. On the contrary, remarkable changes in the contractile activity were found when the extracellular concentration of CaCl2 was reduced from 2.5 to 1.3 or 0.6 mM. In calcium-free solution, the spontaneous contraction was completely abolished. In addition, the phasic contraction was suppressed by CoCl2. Thus, it is assumed that the spontaneous contractile activity of the guinea pig portal vein in hypertonic solution is myogenic in nature and Ca++ plays an essential role in the contraction. On the other hand, diltiazem suppressed the spontaneous phasic contraction in both isotonic and hypertonic solutions. The spontaneously generated and electrically evoked spikes in hypertonic solution were also inhibited by diltiazem. Furthermore, the effects of diltiazem on the mechanical activity and evoked spike were reversed by the addition of CaCl2. Therefore, it is inferred that diltiazem suppresses the spontaneous phasic contraction by inhibiting the mobilization of Ca++ which triggers the generation of the contraction.
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  • Hiroshi WATANABE, Kazuo WATANABE, Koji HAGINO
    1978 Volume 28 Issue 3 Pages 465-472
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Scopolamine-induced locomotor activation was studied in comparison with the responses to apomorphine and methamphetamine in mice. The responses to scopolamine and methamphetamine were markedly depressed by the pretreatment with the catecholamine synthesis inhibitor, α-methyl-p-tyrosine, while the activation response to apomorphine was not affected. p-Chlorophenylalanine did not affect the response to scopolamine. Phenoxybenzamine reduced the responses to scopolamine and methamphetamine, but did not affect the apomorphine response. Propranolol did not affect the responses to the three agonists, scopolamine, apomorphine and methamphetamine. Antipsychotic drugs haloperidol and pimozide reduced the responses to the three agonists. Haloperidol was especially effective in this regard. These results suggest the involvement of catecholamine in the locomotor activation produced by scopolamine. In the rotational behaviour model which is sensitive to dopamine receptor stimulating agents, effects of the three agonists were studied. Scopolamine produced the ipsilateral rotation in mice with unilateral striatal 6-hydroxydopamine-induced lesions. Methamphetamine induced the ipsilateral rotation, while apomorphine produced the contralateral rotation. The rotations induced by three agonists were suppressed by pimozide. The results indicate the participation of dopamine in the scopolamine-induced rotational behaviour in mice.
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  • Norio TAIRA, Toshihiko IIJIMA, Akihiro NARIMATSU, Keisuke SATOH, Teruy ...
    1978 Volume 28 Issue 3 Pages 473-483
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In open-chest dogs the heart rate was controlled at 150 beats/min and drugs were given intravenously. Propranolol (30 μg/kg-1 mg/kg) prolonged the atrio-ventricular (A-V) conduction time and functional refractory period of the A-V conduction system (FRP) by blockade of the existing tone of the sympathetic nerves to the heart. The prolongation of the two parameters by the non-specific depressant action of propranolol was evident only at 3 mg/kg. Propranolol (3-30 μg/kg) shortened the A-V conduction time in the heart deprived of the vagal and sympathetic tone, suggesting some sort of sympathomimetic effect. Pindolol in a wide range of doses (0.3-300 μg/kg) exerted virtually no effect on the A-V conduction time and FRP, and its non-specific depressant action was apparent only at 3 mg/kg. Carteolol slightly prolonged the A-V conduction time and FRP only in low doses (1-10 μg/kg), and in high doses (30 μg/kg-1 mg/kg) it shortened the two parameters, reflecting its predominant sympathomimetic action.
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  • Kazuo AIKAWA, Tetsuo SATOH, Haruo KITAGAWA
    1978 Volume 28 Issue 3 Pages 485-491
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Studies were conducted to determine the in vivo effect of acetaminophen (AAP) on the lipid peroxidation, drug metabolizing enzyme activity and microsomal electron transfer system of rat and mouse liver. AAP was found to inhibit ethylmorphine N-demethylase activity in the presence of NADPH and this inhibition of the enzyme was due to decrease in cytochrome P-450 content, but not due to change in lipid peroxidation in liver microsomes. Kinetical data showed that AAP administration had no effect on Km values of ethylmorphine N-demethylase, however, a decrease in the Vmax values was seen in rats and mice. There was no significant effect of AAP on both NADPH-cytochrome c reductase and the content of cytochrome b5 3 hours after this administration to rats and mice. On the other hand, AAP induced a significant decrease in NADH-ferricyanide reductase in mice, but not in rats. The greatest decrease in cytochrome P-450 was observed among the components of the liver microsomal electron transfer system of rats and mice.
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  • S.S. GAMBHIR, N.K. KAPOOR, P.K. DAS
    1978 Volume 28 Issue 3 Pages 493-495
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Noboru TODA, Mizuo MIYAZAKI
    1978 Volume 28 Issue 3 Pages 495-497
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Sukehiro CHIBA, Edward J. MORETON, Naim KHAZAN
    1978 Volume 28 Issue 3 Pages 498-501
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Yasuyuki NOMURA, Yasue TANAKA, Tomio SEGAWA
    1978 Volume 28 Issue 3 Pages 501-504
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Hajime FUJIMURA, Kaito TSURUMI, Masakatsu NOZAKI, Mikio HORI, Eiji IMA ...
    1978 Volume 28 Issue 3 Pages 505-506
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Heleniee DE SOUZA, Eleonora TRAJANO, Fernando Varela de CARVALHO, Jo&a ...
    1978 Volume 28 Issue 3 Pages 507-510
    Published: 1978
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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