The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 36, Issue 2
Displaying 1-23 of 23 articles from this issue
  • Cletus N. AGUWA, T.R. RAMANUJAM
    1984 Volume 36 Issue 2 Pages 125-129
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Trimipramine, a tricyclic antidepressant, significantly inhibited the development of experimental gastric ulcers induced by various methods like stress, drug (aspirin, reserpine) and Shay's pyloric ligation in an inbred strain of albino rats. Although similar protection was observed with cimetidine, it was found to be ineffective against reserpine-induced ulcers. The antisecretary and ulcer protective effects were not only comparable with that of cimetidine, but even superior in the case of reserpine-induced ulcers. The ability of trimipramine to reduce the ulcer index in various experimental models suggests a centrally mediated effect. Trimipramine appears to be a potentially useful additional therapeutic agent not only because of its anti-ulcer property, but also due to its antidepressive property.
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  • Masaki MAEDA-HAGIWARA, Hiroshi WATANABE, Kazuo WATANABE
    1984 Volume 36 Issue 2 Pages 131-136
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Influences of central alpha-2 adrenergic agonists on thyrotropin-releasing hormone (TRH)-stimulated gastric acid secretion were examined in the perfused stomach of anesthetized rats. Clonidine, an alpha-2 adrenergic agonist, given subcutaneously or intracerebroventricularly inhibited the gastric acid secretion stimulated by intracerebroventricular TRH. Intracerebroventricular injection of norepinephrine tended to reduce the acid secretion, while phenylephrine, serotonin and quipazine (serotonin agonist) did not influence the acid secretion. Subcutaneous clonidine enhanced the acid secretion peripherally stimulated by electrical vagus stimulation. The inhibitory effect of clonidine on TRH-induced acid secretion was reversed by yohimbine, an alpha-2 adrenergic antagonist, and phentolamine. In conclusion, the present study suggests that the central alpha-2 adrenergic receptor system participates in the TRH-mediated central nervous system control of gastric acid secretion in anesthetized rats.
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  • Atsuko INOUE, Yoshihiro NAKATA, Haruaki YAJIMA, Tomio SEGAWA
    1984 Volume 36 Issue 2 Pages 137-145
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    In the present study, we demonstrated the existence of an active uptake system for substance P carboxy-terminal heptapeptide, (5-11)SP. When a fraction from rabbit brain enriched in glial cells was incubated with [3H](5-11)SP, an uptake of [3H](5-11)SP was observed. The uptake system has the properties of an active transport mechanism. Kinetic analysis indicated two components of [3H](5-11)SP uptake, one representing a high and the other a low affinity transport system. After unilateral ablation of the striatum, approximately 30% of the high affinity [3H](5-11)SP uptake capacity of substantia nigra slices disappeared. The subcellular distribution of the high affinity uptake indicated that [3H]5-hydroxy-tryptamine was taken up mostly into the P2B fraction (synaptosomal fraction), whereas [3H](5-11)SP was taken up into the P2A fraction (myelin fraction) to the same extent as into the P2B fraction. These results suggest that when SP is released from nerve terminals, it is hydrolysed into (5-11 )SP, which is in turn accumulated into glial cells as well as nerve terminals and that this high affinity uptake mechanism may play an important role in terminating the synaptic action of SP.
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  • Ee-Kiang GAN, Alias ABAS, Aishah LATIFF
    1984 Volume 36 Issue 2 Pages 147-151
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    Effect of chronic angiotensin converting enzyme blockade on the pressor response to exogenous angiotensin II, noradrenaline and vasopressin were evaluated in DOCA-salt induced hypertensive rats using teprotide. The blood pressure of rats receiving teprotide chronically was reduced markedly. The pressor responses to exogenous angiotensin II was accentuated, while that of noradrenaline and vasopressin were significantly reduced. It is concluded that besides the angiotensin converting enzyme blocking action, the decrease in sensitivity of the pressor response to noradrenaline and vasopressin may contribute towards the antihypertensive activity of teprotide given chronically.
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  • Satoshi KASHII, Juichi ITO, Izuru MATSUOKA, Masashi SASA, Shuji TAKAOR ...
    1984 Volume 36 Issue 2 Pages 153-159
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    Electrophysiological studies were performed to elucidate the effects of ethanol on neuron activities in the lateral vestibular nucleus (LVN) and medial vestibular nucleus (MVN) of cats using an electrosmotic and microiontophoretic method. The LVN and MVN neurons were classified into two types according to the firing pattern and latency of the first spike with vestibular nerve stimulation: monosynaptic and polysynaptic neurons. Electrosmotic application of ethanol up to 200 nA produced a dose-dependent inhibition of spikes of the LVN monosynaptic neurons with vestibular nerve stimulation and iontophoretically applied glutamate, but no significant alterations of the spikes of the LVN polysynaptic neurons. Acetylcholine-induced firing in the LVN monosynaptic neurons was also inhibited by ethanol. In the MVN, spike generation of the monosynaptic and polysynaptic neurons with vestibular nerve stimulation and iontophoretically applied glutamate remained unaltered with ethanol up to 200 nA. These results indicate that ethanol predominantly inhibits synaptic transmission of the LVN monosynaptic neurons, probably by acting on the postsynaptic cell bodies.
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  • Fumitaka KIKKAWA, Takahide NOMURA, Yasumichi HAGINO
    1984 Volume 36 Issue 2 Pages 161-167
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Nature of cyclic AMP-dependent protein kinases from the uterus of euthyroid and hypothyroid estrus rats was investigated. There was no significant difference between euthyroid and hypothyroid rats in the protein content and the total activity of cyclic AMP-dependent and independent protein kinases of the soluble fractions of uterus tissues. However it was clearly demonstrated that the type I isozyme remarkably decreased in hypothyroid rats in comparison with that of euthyroid rats. The ratio of type I to type II was 1.26 in euthyroid rats and 0.41 in hypothyroid rats. The kinetic properties of the type I and the type II isozymes from both groups of rats showed similar patterns in NaF, Mg2+, cyclic AMP, histone and ATP. It was not observed that the apparent Km values of both the isozymes for histone and ATP were significantly different between euthyroid and hypothyroid rats. Data obtained from these experiments suggested that the thyroid hormone affected the metabolic processes of the uterus through alteration of the isozyme distribution of cyclic AMP-dependent protein kinase.
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  • Motoki KOBAYASHI, Katsuya OHATA
    1984 Volume 36 Issue 2 Pages 169-175
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Four uterine-contractile substances (a, b, c and d) and three uterine-contractile substances (a', c' and d') were obtained from the reaction mixture of rat plasma kininogen with the kinin-forming enzyme in rat stomach and the homogenate of the rat stomach with 0.2% acetic acid, respectively. By high performance liquid chromatography with a Zorbax ODS reversed-phase column, the retention times of materials a, c and d were found to be equal to those of materials a', c' and d', and they were not equal to those of kallidin, methionyl-lysyl-bradykinin (MLBK) and bradykinin (BK). The retention time of material b was equal to that of BK. The uterine-contractile activities of the materials a, b, c, d, a', c' and d' were all abolished by chymotrypsin, but not by trypsin treatment. These materials all relaxed the isolated rat duodenum in the presence of atropine, dibenamine, diphenhydramine and propranolol, and they produced a fall in rabbit blood pressure after administration of atropine, dibenamine and propranolol. The content ratios of a: b: c: d and a': c': d' were 4: 4: 67: 25 and 65: 19: 16, respectively, as calculated from the uterine-contractile activities of these materials.
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  • Shigeru OKUYAMA, Hironaka AIHARA
    1984 Volume 36 Issue 2 Pages 177-186
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    A single neuronal activity was recorded extracellularly in the ventrobasal (VB) nucleus of the thalamus in adjuvant arthritic rats under urethane anesthesia (1200 mg/kg, i.p.). The effects of morphine and indomethacin on the evoked responses elicited by noxious stimuli (transcutaneous electrical stimulation and tibial nerve electrical stimulation) and/or non-noxious stimuli were investigated. Intravenous administration of morphine and indomethacin depressed the evoked responses elicited by either transcutaneous electrical stimulation or tibial nerve electrical stimulation without affecting any backgroud activities. By contrast, the responses of all neurones investigated responding to non-noxious stimuli were never depressed by the intravenous administration of morphine and indomethacin. Morphine showed the same depressant effects on the evoked responses activated by both noxious stimuli, but the depressant effects due to indomethacin on the evoked discharges were more sensitively produced by transcutaneous electrical stimulation than tibial nerve electrical stimulation. Depressant effects of morphine were restored by intravenous naloxone administration, but not observed in case of indomethacin. These results suggest that an analgesic mechanism of morphine and indomethacin may reside in the neo-spinothalamic projection system of adjuvant arthritic rats and that the site of action of indomethacin may also reside in a peripheral site. However, the mode of the central action of indomethacin was different from that of morphine.
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  • Shinya WAKUSAWA, Kenichi MIYAMOTO, Ryozo KOSHIURA
    1984 Volume 36 Issue 2 Pages 187-195
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    We investigated the effect of reserpine on the antitumor effect of vinblastine (VBL) with regard to the drug resistance of rat ascites hepatomas. The sensitivity to VBL was in the order of AH13>AH44>AH109A>AH66 cells in the in vitro growth-inhibitory test, and AH66 cells were inherently most resistant to VBL. The intracellular accumulation of VBL was lower in resistant cells than in sensitive cells. Reserpine increased the sensitivity to VBL in the order of AH66>AH109A>AH44>AH13 cells. The antitumor synergism was also observed in the in vivo experiments using AH44 and AH66. Reserpine enhanced the VBL accumulation more than 2 times in AH66 and AH109A cells, but slightly increased it in AH13 and AH44 cells. These results indicated that the synergistic effect of reserpine was more potent in relatively resistant cell lines to VBL, and the effect was caused by the enhancement of VBL accumulation. On the other hand, the enhanced growth-inhibitory effect and the accumulation of VBL in the presence of reserpine were not influenced by further preincubation with reserpine. Reserpine also did not influence the intracellular level of VBL increased by 2, 4-dinitrophenol in a glucose deprived medium. Reserpine decreased the VBL extrusion from AH66 cells more strongly than that from AH44 cells. These results indicated the possibility that reserpine interfered with the VBL efflux process, while it might not influence the VBL influx process. In conclusion, reserpine potentiated the effect of VBL on resistant ascites hepatoma cells more than on sensitive cells, and the synergistic effect of reserpine could be explained by the inhibition of VBL efflux and VBL accumulation in tumor cells.
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  • Tadahiro SHIKIMI, Youko TANABE, Keisuke HATTORI
    1984 Volume 36 Issue 2 Pages 197-203
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Following preincubation of aprotinin with gelatin, the inhibitory effect on the trypsin activity was enhanced under the same condition as in the case of enhanced antigen-antibody reaction of aprotinin in gel in the presence of gelatin. In the immunochemical titration of aprotinin, gelatin treatment decreased the value of the equivalence point of aprotinin. Immunoprecipitation of aprotinin pre-incubated with or without gelatin adjusted to equal activity per unit volume resulted in overlapping equivalence points. These data suggest that the increase in aprotinin activity in the presence of gelatin is due to increase in the active form of aprotinin.
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  • Yoshihiro HOTTA, Hiroaki ANDO, Naohiro SHIRAI, Jinsaku SAKAKIBARA, Kaz ...
    1984 Volume 36 Issue 2 Pages 205-215
    Published: 1984
    Released on J-STAGE: November 07, 2006
    JOURNAL FREE ACCESS
    Interrelation between lipophilic characters and speeds of positive inotropic effect (PIE) of cardenolides and ericaceous toxins was studied by determining both parameters of lipophilicity and inotropy speeds. The lipophilic characters of 8 kinds of cardenolides, evaluated from RMm, or log k' values by means of thin layer chromatography (Rf) or high performance liquid chromatography (retention time), increased in the order of ouabain, digoxin, digitoxigenin, digitoxigenin-mono-digitoxoside, digitoxigenin-bis-digitoxoside, digitoxin, α-acetyl-digitoxin, triacetyl-digitoxin. Lipophilic character, evaluated from Rm values of 6 kinds of ericaceous toxins, was in decreasing order of 10S-grayanotoxin II, 6-acetyl grayanotoxin I, asebotoxin I, grayanotoxin I, asebotoxin III, asebotoxin X. The speed with which PIE developed was evaluated from the time to half maximum PIE (T50) of cardenolides and ericaceous toxins at a pD2 concentration. The speed of positive inotropy of cardenolides was independent of their concentration tested in the range from half to twice the concentration of pD2, while the speeds of PIE of ericaceous toxins depended on their concentration in the same range used in case of cardenolides. Inotropy speed of these two classes of cardiotoxins correlated well with the lipophilic character: a) In the case of cardenolides, a positive and close correlation (r=0.98) was observed between T50 and Rm. The more lipophilic the cardenolides, the more time was required to reach the fully development of PIE. b) In contrast, a negative correlation (r=-0.82, between Rm and T50) was obtained in the case of ericaceous toxins; Toxins with more lipophilic nature caused faster development of PIE. The present results can be interpreted to mean that the PIE receptor for cardenolides in myocardial cells is located on the outer surface of the sarcolemma, while that for ericaceous toxins is located on the inside of the myocardial cell.
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  • Kimio KARIYA, Eibai LEE, Masaaki HIROUCHI
    1984 Volume 36 Issue 2 Pages 217-222
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    The relationship between the toxic effect of propylthiouracil (PTU) and myeloperoxidase activity of rat bone marrow was examined. The administration of PTU for 1 or 2 weeks caused a decrease in leukocyte count with the concomitant inhibition of the activity of myeloperoxidase in the bone marrow. The decreases in both leukocyte counts and myeloperoxidase activity were restored to control levels at 2 weeks after the discontinuation of the administration. PTU treatment did not affect the affinity of H2O2 for the enzyme; however, an increase in the Km value for guaiacol was seen. PTU, incubated with bone marrow peroxidase in vitro increased the Km value of the enzyme for guaiacol, but had no effect on the Km value for H2O2. The results suggest that the mechanism of inhibition of myeloperoxidase activity by PTU given in vivo or incubated with the enzyme in vitro may be the same. The activity of bone marrow glutathione peroxidase was not influenced by PTU treatment.
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  • Masahiro TSUCHIMOTO, Keiji KOMORIYA, Tamotsu KOYAMA, Kenji HOSODA, Tor ...
    1984 Volume 36 Issue 2 Pages 223-234
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    Acute glomerulonephritis characterized by proteinuria, hypoalbuminemia and leukocytosis was induced in mice by repeated intraperitoneal injections of calf serum (1 ml/mouse×10). In mice treated with calf serum, hypercellularity, karyorrhexis, expansion of the mesangium and hyalinosis in the glomeruli were observed by light microscopy. Furthermore, circulating immune complexes were detected in the serum, and deposits of mouse IgG and C3 on the basement membranes of the glomeruli were demonstrated immunohistochemically. Oral administration of cyclophosphamide or 6-mercaptopurine at a dose of 20 mg/kg/day significantly suppressed the development of this nephritis. Dexamethasone (0.5 mg/kg/day) caused moderate inhibition of the nephritic changes. These results suggest that this experimental model may be useful for evaluation of anti-nephritic drugs.
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  • Satoshi AKABANE, Shunichi KOJIMA, Keiichi ITO, Minoru KAWAMURA
    1984 Volume 36 Issue 2 Pages 235-240
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    To examine the role of endogenous angiotensin II or kinins in the mechanism of the increased renal vascular reactivity to exogenous angiotensin II following acute blood volume expansion, we examined whether captopril, a converting enzyme inhibitor, can prevent the increase in renal vascular response in anesthetized dogs. Pretreatment of dogs with captopril increased plasma renin activity, but it did not affect systemic blood pressure, renal blood flow and renal vascular resistance. Acute blood volume expansion with saline suppressed plasma renin activity in dogs with or without pretreatment with captopril. Basal level of renal vascular reactivity to angiotensin II was increased by pretreatment with captopril. In the control animals, acute blood volume expansion enhanced renal vascular reactivity to angiotensin II but not norepinephrine. The enhanced renal vascular reactivity to angiotensin II, however, was not prevented by the captopril treatment. The failure of captopril to prevent an increase in renal vascular reactivity to angiotensin II following acute blood volume expansion was associated with an increase in urinary excretion of bradykinin. These data suggest that endogenous angiotensin II level is not necessarily a determinant for vascular reactivity to exogenous angiotensin II, especially in the case of acute blood volume expansion.
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  • Tomokazu HOSOKAWA, Kazuhiro GOTO, Junzo KAMEI, Kokichi OHTANI, Miwa MI ...
    1984 Volume 36 Issue 2 Pages 241-248
    Published: 1984
    Released on J-STAGE: November 07, 2006
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    We devised a preparation for measuring the vagal reflex tracheal constriction following the bronchoconstriction induced by histamine inhaled in the bronchial side in dogs. Properties of the vagal reflex tracheal constriction were investigated using this preparation. Histamine inhaled in the bronchial side caused the tracheal constriction following the bronchoconstriction. The tracheal constriction was inhibited by section of the bilateral superior laryngeal nerves or vagal cooling, respectively, but was not completely blocked. The combination of section of the bilateral superior laryngeal nerves and vagal cooling abolished the tracheal constriction. An i.v. administration of pentobarbital reduced both bronchoconstriction and tracheal constriction. These findings indicate that the tracheal constriction observed in the present study is mediated by the vagal reflex arc and that the extravagal pathway consisting of the recurrent and superior laryngeal nerves plays a role in a part of the afferent pathway of the vagal reflex airway responses. When the bronchoconstriction was completely abolished by isoproterenol inhaled in the bronchial side, the reflex tracheal constriction still existed. Transient inflation and deflation of the lungs caused reflex tracheal dilatation and constriction, respectively. We conclude that the vagal reflex airway constriction is due to complex effects which may be mediated by plural sensory receptors in the airways.
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  • D.K. GANGULY, H.-G. ROSS, S. CLEVELAND
    1984 Volume 36 Issue 2 Pages 249-252
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Noboru TODA, Mizuo MIYAZAKI, Tomio OKAMURA
    1984 Volume 36 Issue 2 Pages 253-255
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Yoshio OHMIYA, Harihara M. MEHENDALE
    1984 Volume 36 Issue 2 Pages 256-257
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Shinichi HATTA
    1984 Volume 36 Issue 2 Pages 258-261
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Ken-Ichi SAITO, Masayoshi GOTO, Hideomi FUKUDA
    1984 Volume 36 Issue 2 Pages 262-264
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Masanori KAWAI, Takashi SAKAUE, Chiemi WATANABE, Yasuyuki NOMURA, Tomi ...
    1984 Volume 36 Issue 2 Pages 265-267
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Yasuo MATSUMURA, Nobuaki MIYAWAKI, Shiro MORIMOTO
    1984 Volume 36 Issue 2 Pages 268-271
    Published: 1984
    Released on J-STAGE: November 07, 2006
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  • Akemichi BABA, Yoshihiro KUMAGAE, Tohru TATSUNO, Heitaroh IWATA
    1984 Volume 36 Issue 2 Pages 272-274
    Published: 1984
    Released on J-STAGE: November 07, 2006
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