The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 25 , Issue 6
Showing 1-22 articles out of 22 articles from the selected issue
  • Saizo YANAURA, Tomoo NISHIMURA, Mitsuo SAKAMOTO, Tetsuo SASAO
    1975 Volume 25 Issue 6 Pages 621-629
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    To investigate the role of bronchoconstriction in the cough reflex, we compared antitussive effects of several drugs with their ability to effect the respiratory tract (i.e. bronchodilatation vs. bronchoconstriction). Antitussive activities of five drugs administered either intravenously or orally on electrically-induced cough were evaluated in the non-anesthetized dog. The antitussive activities were as follows: morphine, 0.1 mg/kg (i.v.) and 0.5 mg/kg (p.o.); codeine, 1.0, 4.0; picoperidamine, 2.0, 9.8; piclobetol, 7.6, 9.0; HH-197, 12.5, 143.0, respectively. Morphine, codeine and HH-197 caused bronchoconstriction, but picoperidamine and picrobetol caused bronchodilatation. The antitussive and bronchodilatation effects of isoproterenol were abolished by propranolol. Each bronchoconstricting drug (i.e. morphine, codeine and HH-197) was administered concurrently with isoproterenol (10 μg/kg, i.v., and non-antitussive activity), and the cough reflex was observed. Compared with the single administration of each drug, respiratory resistance was decreased and the anti-tussive effect was increased. These results indicate a strong correlation between bronchodilatation and increased antitussive activity.
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  • Fikry H. Osman, E.M. Ammar
    1975 Volume 25 Issue 6 Pages 631-637
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    When studying some of the properties of 5-hydroxytryptamine (5HT) receptors in the rat uterine muscle using phenoxybenzamine (PBZ) as an antagonist it was found that the specific receptors for 5HT in the smooth muscle were selectively blocked by PBZ; a period of 20-minute exposure to the antagonist was required for maximal effect. The blockade produced was of long duration and the recovery of response was relatively slow; it was incomplete throughout the 4-hour observation period. A concentration of 1 × 10-8 g/ml PBZ produced a parallel shift of the doseresponse effects while higher concentrations reduced both the slope and maximal response. The reasons for such a shift were discussed. 5HT produced a rapid onset and offset of effect suggesting that the site of 5HT receptor is on the surface of the cell membrane. Moreover, 5HT could protect its own receptor against PBZ blockade.
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  • Isami SHUDO, Hideya SAITO, Tsuneyoshi TANABE
    1975 Volume 25 Issue 6 Pages 639-643
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    The action of ouabain on myocardial inotropism pretreated with 6-hydroxydopamine and α-methyl-p-tyrosine was studied. Inotropic action of ouabain was not changed by depletion of catecholamines in the brain, in which the central sympathetic neurons were destroyed by an intraventricular administration of 6-hydroxydopamine. Systemic administration of 6-hydroxydopamine and α-methyl-p-tyrosine reduced ventricular catecholamines to 5.3% and 20.8% of the control, respectively. Percent increase of contractility by ouabain after the pretreatment of 6-hydroxydopamine and α-methyl-p-tyrosine was reduced to 16.7% and 50.2% of the control, respectively. The results obtained suggest that catecholamines in the myocardium play some important role in producing cardiotonic action of cardiac glycosides. Brain catecholamines or the central sympathetic nervous system do not appear to participate in the exertion of the positive inotropic action of cardiac glycosides.
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  • Hiroko SATOH, Yukio KUROIWA
    1975 Volume 25 Issue 6 Pages 645-652
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Effects of normal rabbit. IgG (N-IgG) and phenobarbital specific IgG (Ab-IgG) on cyclobarbital-induced sleeping time were studied. Ab-IgG was specifically purified by Immunoadsorbent from rabbit antisera obtained by immunization with p-azophenobarbital bovine gamma globulin. N-IgG was purified from normal rabbit sera by DEAE-cellulose chromatography. The aggregate-free IgG were passively immunized to C3H mice 1 hr before intraperitoneal injection of cyclobarbital which has a high binding affinity to the antibodies. The pretreatment with N-IgG prolonged significantly cyclobarbital-induced sleeping time as compared with that of saline treated group, however, in the Ab-IgG treated group the duration of the sleeping was much the same as that seen in the saline group. To determine whether Ab-IgG has any influence on barbiturate tolerance, effects of N-IgG and Ab-IgG on the activities of hepatic enzymes in 9, 000 g supernatant (alkaline RNase and aminopyrine demethylase) of the mice were examined at 40 hours after cyclobarbital administration. The activities of both enzymes which could he induced by cyclobarbital were decreased significantly in Ab-IgG treated group as compared with those of N-IgG group. These results are discussed with relation to barbiturate tolerance.
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  • Tsukasa SAKURADA, Kenji ONODERA, Takeshi TADANO, Kensuke KISARA
    1975 Volume 25 Issue 6 Pages 653-661
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Effects of polyamines on the central nervous system were studied in mice. Intraperitoneal administration of Spermidine (SPD) and Spermine (SPM) decreased spontaneous motor activity as measured by either the photo-cell counters method or the open-field test and lowered rectal temperature. A significant prolongation of sleeping time after pentobarbital was confirmed in small doses of SPD and SPM which had slight influence on spontaneous motor activity. The time to convulsion and death induced by strychnine was elongated by SPD and SPM. SPM in small doses inhibited writhing responses induced by 0.7% acetic acid. In addition, methamphetamine-induced hyperactivity and conditioned avoidance response were blocked by SPM in doses which decreased spontaneous motor activity. In all experiments, SPM appeared to have a powerful pharmacological activity compared with SPD. LD50 for SPD and SPM was 620 (500-769) mg/kg i.p. and 310 (200-480) mg kg i.p., respectively.
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  • Yuichi FUJII, Yasuo ISHII
    1975 Volume 25 Issue 6 Pages 663-670
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    The cysteamine-induced duodenal ulcer reported by Selye et al. was investigated and the optimum conditions for the production of ulcers in rats were established. A single subcutaneous administration of cysteamine between 200 and 500 mg/kg produced ulceration in a dose-dependent manner in the duodenum within 18 hr. Female and older rats were more susceptible to cysteamine than male and younger ones, respectively. Atropine methylbromide inhibited duodenal ulcers induced by cysteamine dose-dependently and pyloric ligation immediately prior to cysteamine dosing completely inhibited ulceration. Tetragastrin or bethanechol increased the severity of cysteamine-induced ulceration. These data suggest that gastric juice may play an important role in the pathogenesis of cysteamine-induced ulcers. The present study provides an excellent animal model for studying the mechanism of duodenal ulcers and screening of antiulcer agents.
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  • Masahiro MORI, Yutaka SAKAI
    1975 Volume 25 Issue 6 Pages 671-680
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Reflex responses in the recurrent laryngeal (RL) nerve to stimulation of the superior laryngeal (SL) nerve and the effects of antitussive drugs on these reflex responses were studied in order to elucidate the site of action of these drugs in encéphale isolé cats. The RL nerve fibers were classified into four types by discharge patterns in respect to phases of artificial ventilation; type I: no spontaneous discharges, type II: discharges in phase with inflation of the lung, type III: discharges in phase with deflation of the lung, type IV: tonic discharges. Repetitive stimulation of the SL nerve elicited tonic burst discharges or short burst discharges in all types of RL nerve, while the same procedure inhibited ongoing discharges of the type III and IV fibers only. The inhibited fibers tended to have slow conduction velocities (20-80 m/sec). Administration of antitussive drugs such as codeine, dextro methorphan and oxymetebanol as well as pentobarbital decreased the frequency of the after spike dischargesin the RL nerves evoked following repetitive shocks to the SL nerve, but had no effects on the inhibition of RL nerve discharges evoked by the stimulation of the same nerve. The neuropharmacological implication of these findings as related to the cough reflex are discussed.
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  • Naohisa ISHIKAWA, Yasumichi HAGINO, Tatsuro SHIGEI
    1975 Volume 25 Issue 6 Pages 681-686
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Searching for an experimental condition to produce pulmonary edema of uniform high grade severity in rabbits, five different doses of epinephrine (38, 60, 100, 160 and 260 μg/ml) were infused at a rate of 0.29 ml/min for 20 min into the femoral vein of fed and fasted animals. Body temperature was maintained at 38 to 40°C. The incidence of pulmonary edema was not dose-dependent, and was approx. 70% by the administration of 60 to 260 μg/ml of epinephrine solutions. In general, the edema was more severe in the fed group than in the fasted. The highest dose of epinephrine was often fatal in the fasted group. One hundred μg/ml (approx. 10 μg/kg/ min), fed was regarded as a favourable condition for the experiment. The amounts of lung lipids increased in edema (+) cases of the fed groups. The plasma potassium level was elevated in proportion to the dose of epinephrine. The clotting time of blood was markedly prolonged in edema (+) rabbits. The significance of these observations was discussed in regard to the mechanism of epinephrine-induced pulmonary edema.
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  • Susumu OKABE, Koji TAKEUCHI, Tetsuro URUSHIDANI, Toshihiko NAGANUMA, K ...
    1975 Volume 25 Issue 6 Pages 687-691
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Cirrhosis of the liver in rats was induced by the administration of carbon-tetrachloride (0.1 ml/100 g of body weight, s.c.) biweekly for 13 weeks. In the pylorus ligation preparation, acetylsalicylic acid (ASA) 100 mg/kg p.o. Induced much more serious gastric damage in CCl4-induced cirrhotic rats as compared with rats with a normal liver. L-glutamine 750 mg/kg p.o. prevented the ASA-induced gastric lesions in both normal and cirrhotic rats, even though the degree of the inhibition was weaker in cirrhotic rats. Gastric analysis indicated that L-glutamine 750 mg, , kg p.o. markedly inhibited the gastric ionic changes (acid back diffusion) in response to ASA in both cirrhotic and normal rats.
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  • Futoshi IZUMI, Simon FREED
    1975 Volume 25 Issue 6 Pages 693-707
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Proteolipids from rat cerebral cortex quenched at -196°C were extracted and fractionated at subzero temperature (-60°C). On Sephadex LH-20 column chromatography, acetylcholine and cholinergic blocking agents such as dimethyl-d-tubocurarine and decamethonium were observed to bind to different fractions of proteolipids showing that the receptor fractions for acetylcholine and that for cholinergic blockers need not be the same. The acetylcholinesterase (EC 3.1.1.7) activity was demonstrated to be absent in both types of receptor fraction. The specificities of binding by cholinergic substances to proteolipid fractions prepared at -60°C persisted at room temperature with some loss in specificity for acetylcholine. Since these specificities were not observed in previously reported experiments at room temperature, it appears that the structures of proteolipids extracted at the two temperatures differ. The appearance of specificities in the proteolipids prepared at low temperature suggest that their structures are in better approximation to those in vivo that presumably are highly specific. The importance of the protein moiety of proteolipids as a discriminator for the neurotransmitter is discussed.
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  • Hiroshi IZUMI, Hikaru OZAWA
    1975 Volume 25 Issue 6 Pages 709-718
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    A study was made of the effects of various agents on adenylate cyclase in synaptosomes in both the absence and presence of the boiled supernatant from rat cerebral cortex. The activity of adenylate cyclase in these preparations was inhibited by the sulfhydryl reactive agent p-chloromercuribenzoate. Sulfhydryl compounds such cysteine, glutathione and Coenzyme A stimulated the enzymic activity in both the absence and presence of the boiled supernatant. The chelating agent 1.2-bis-(2-dicarboxymethylaminoethoxy)ethane caused a stimulation of the enzymic activity with and without the presence of the boiled supernatant. Adenine nucleotide (adenine, adenosine, AMP and ADP), GTP, Pi and carbamylcholine seemed to have little effect. The stimulatory substance in the boiled supernatant was estimated to have a molecular weight in the range of 1, 000-1, 300.
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  • Yukio ISHIDA, Noriaki KONDO, Shunzo AIHARA, Hideyuki NAKAGAWA
    1975 Volume 25 Issue 6 Pages 719-726
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Dehydroepiandrosterone (DEA), a metabolite of steroid hormone in the urine, differed from papaverine in the mode of inhibitory action on the isolated guinea-pig ileum. Papaverine inhibited both phasic and tonic contractions induced by an agonist, while DEA inhibited the phasic contraction without apparent fatigue of the tonic phase. The main action of papaverine seems to be predominatly a metabolic inhibition similar to that of metabolic inhibitors, but the action of DEA could not be ascribed to that of metabolic inhibition. In the presence of papaverine or metabolic inhibitors the height of maximal contraction of an agonist tested by the cumulative method was greatly depressed and less than that by a single method. The longer the time involved in the cumulative doses, the lower was the maximal contraction.
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  • Tadahiko KARASAWA, Kiyoshi FURUKAWA, Kouichi YOSHIDA, Masanao SHIMIZU
    1975 Volume 25 Issue 6 Pages 727-736
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    A double column procedure was devised for simultaneous estimation of norepinephrine, normetanephrine, dopamine, 3-methoxytyramine, and 5-hydroxy-tryptamine in brain tissue. Columns of aluminum oxide were placed on columns of Amberlite CG-50 by use of a specially devised column holder so that the effluent from the upper columns could flow directly into the lower ones. Perchloric acid extracts of brain samples were passed through the doubled columns after the pH was adjusted with K2CO3. Norepinephrine and dopamine in the extracts were adsorbed on aluminum oxide in the upper columns while normetanephrine, 3-methoxytyramine, and 5-hydroxytryptamine were retained by Amberlite CG-50 placed under the aluminum oxide columns. The amines adsorbed on both columns were eluted in a small volume of dilute HCl and each of the amines was determined fluorometrically. Some modifications were incorporated into the existing methods for developing fluorescence from the amines to increase the sensitivity. The recovery rate throughout the entire procedure for the authentic amines added to brain homogenates was in the neighborhood of 90% or higher with little column to column variation. The procedure was tested in the estimation of the five amines on various parts of single brains of normal or pargyline-treated rats.
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  • Kazuo NAKAGAWA, Kinya KURIYAMA
    1975 Volume 25 Issue 6 Pages 737-746
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    When rats were exposed to immobilized cold stress, adrenaline content in the adrenal gland as well as noradrenaline content in the brain stem were reduced drastically, while noradrenaline content in the atria was not altered by the application of stress. Oral administrations of taurine (4-7 g/kg/day, for 3 days) prevented the stress-induced decline of adrenaline in the adrenal gland and this preventive effect could not be duplicated by the administration of L-isoleucine or DL-methionine. In hypophysectomized rats, the stress also induced a significant fall in adrenaline content of the adrenal gland, however taurine administration did not show significant preventive effects on the decline in adrenal catecholamines. The immobilized cold stress induced a significant increase in blood sugar and this increase was antagonized by pretreatment with taurine. Taurine had no significant effects on the stress-induced increase in the activity of adrenal tyrosine hydroxylase and the turnover rate of adrenaline in the adrenal gland measured by the rate of decline of this amine following α-methyl-tyrosine administration. The administration of taurine, in both in vivo and in vitro, inhibited the release of adrenaline from adrenal medullary granules, but that of dopamine-β-hydroxylase was not significantly affected. The stress-induced elevation of the blood level of corticosterone was not affected by taurine administration. These findings indicate that taurine antagonizes the stress-induced elevation of blood sugar by reducing adrenaline output from the adrenal gland. The regulatory mechanism most likely involves the inhibition of adrenaline release from adrenal medullary granules, possibly by stabilizing the membrane of the granules.
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  • Tomonobu TOKIWA, Ieaki UEMURA, Hironori MURAKAMI, Sonoko TSURUOKA, Mas ...
    1975 Volume 25 Issue 6 Pages 747-762
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    35S-Caerulein (35S-F16934) was administered intramuscularly into rats (280 μg/kg), rabbits (380 μg/kg) and mice (3.3 mg/kg). Blood level of radioactivity in rats and rabbits reached the maximum at 5 and 15 min after administration, respectively, and then decreased rapidly. In both rats and rabbits, the radioactivities were excreted mainly into the urine. The physiological activity of F16934 was detected in the blood of rats and rabbits collected within 15 and 30 min after injection respectively, and in the bile of rats collected within the first 2 hr. In rats, the radioactivities were densely distributed in kidney, liver, pancreas, and intestine. Four metabolites of 35S-FI6934 were isolated by paper chromatography from rat urine (i.m., 500 μg/kg). The main metabolites, F-I and F-II, were negative to nynhydrin and to the Ehrlich reagent and carried no physiological activity. 35S-Chym-I, which was prepared by digesting 35S-F16934 with chymotrypsin, was injected to rats (i.m. 16 or 8 mg/kg). The metabolite, C-I, isolated from the urine was considered to have a very similar structure to F-I from the results of paper chromatography and paper electrophoresis. By amino acid analysis. the structure of C-I was estimated to be as follows:
    Pyr-Gln (or Glu)-Asp-Tyr-Thr-Gly
    ¦
    SO3H
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  • Hiroichi NAGAI, Kunio OSUGA, Akihide KODA
    1975 Volume 25 Issue 6 Pages 763-772
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
    Baicalein, a flavonoid, is anti-allergic but only slightly soluble in water. The soluble derivatives of baicalein, disodium baicalein-6-phosphate (BPS) and sodium baicalein-6-sulfate (BSS), were synthesized and examined regarding their effects on hypersensitivity reactions. These derivatives inhibited type I and II reactions as classified by Coombs and Gell. The Arthus reaction belonging to type III reaction, however, was hardly affected with either BPS or BSS. The experimental asthma caused by passive systemic anaphylaxis in guinea pigs was prevented with application of BPS. Thus even by the oral route, BPS appears to be clinically applicable to extensive allergy related diseases.
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  • Yasuyuki NOMURA, Fumiko NAITOH, Tomio SEGAWA
    1975 Volume 25 Issue 6 Pages 773-779
    Published: 1975
    Released: December 19, 2006
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    Norepinephrine(NE), dopamine(DA) and serotonin(5-hydroxytryptamine, 5-HT) contents were estimated in the different regions of the developing rat brain following guanethidine injection at the neonatal period for the purpose of determining the influence of guanethidine on development of the monoamine neuron in the brain. Despite a nonsignificant change in the weights of all regions of the brain, guanethidine caused a significant reduction of NE content in the limbic-striatum at day 7 and 30 and an increase in mesencephalon-ponsmedulla at day 30. DA concentration in the limbic-striatum at day 7, 14 and 30 and in the neocortex at day 7 showed a decrease with guanethidine treatment. The change in 5-HT content was not induced with guanethidine in all regions and all days examined. These results suggest that guanethidine, crossing the blood-brain barrier at the neonatal stage, induced the degeneration of the nerve terminals and ‘collateral accumulation’ of catecholamines in the central NE and DA neurons.
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  • Kaito TSURUMI, Hajime FUJIMURA
    1975 Volume 25 Issue 6 Pages 781-784
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
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  • Tsutomu KAMEYAMA, Tsuyoshi SHIGEHISA, Toshitaka NABESHIMA
    1975 Volume 25 Issue 6 Pages 784-787
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
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  • Yoshimi MISU, Yasushi KURAISHI, Hiroshi TAKAGI
    1975 Volume 25 Issue 6 Pages 787-790
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
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  • Yoshiaki GOTO, Kazuo WATANABE
    1975 Volume 25 Issue 6 Pages 790-793
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
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  • Tetsuya KAMATAKI, Kazuo AIKAWA, Naoki OZAWA, Haruo KITAGAWA
    1975 Volume 25 Issue 6 Pages 793-796
    Published: 1975
    Released: December 19, 2006
    JOURNALS FREE ACCESS
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