The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 21, Issue 2
Displaying 1-15 of 15 articles from this issue
  • Takashi HISAMATSU, Tadashi NAKAZAWA, Takemi KOEDA
    1971 Volume 21 Issue 2 Pages 139-154
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    2: 2-Diphenyl-4-N-hexamethylenimino-butyramide methiodide (R-661) is one of the series of substituted diphenylpropyl-amines synthesized by Janssen et al. and is a typical quaternary atropine-like substance (1-9). It has anticholinergic activity, namely, parasympatholytic activity.
    Additionally, Janssen et al. reported that this compound showed the excellent gastrointestinal absorption and inhibited the formation of experimental gastric ulcer in rats (9). In the present experiments, an attempt was made histo-pharmacologically to evaluate the curative effect of R-661 on experimental ulcers in glandular stomachs of rats.
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  • Tadao OKAMURA
    1971 Volume 21 Issue 2 Pages 155-166
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The mechanism of the anaphylactic contraction of smooth muscle have ever been discussed by several investigators. But the fundamental question have never been solved clearly; whether the anaphylactic contraction of smooth muscle can be produced by the direct effect of antigen-antibody reaction on the cell membrane and/or on the contractile elements in the cell or not? This is the most interesting and without dealing with it, anaphylactic contraction is hardly said to be completely studied. Some problems have recently been brought foreward in the “chemical mediator theory”. Many substances are advocated as “chemical mediators”, acetylcholine, histamine, serotonin, bradykinin, slow reacting substance in anaphylaxis, plasmine, ATP and so on (1, 2). There is, however, no established view as to what is essential in anaphylaxis, and whether it is a single or plural. The chemical mediator theory seems to be supported only the fact that in anaphylaxis, endogenous chemical substances are increased in blood over the normal level, and that the symptom in anaphylaxis is resemble with that introduced by administration of such a substance.
    On the other hand, the observations in the electrophysiological study have recently given me some important informations about a relation between excitability of cytoplasmic membrane and muscular contraction (3-8). In 1958, Evans et al. (9) reported that acetylcholine, histamine and serotonin could induce contraction of the smooth muscle even which cytoplasmic excitability was abolished by the “isotonic potassium-Ringer”. The present work was undertaken to elucidate this point in anaphylactic contraction in smooth muscle and for this purpose, changes in membrane potential and tension of the muscle were recorded during antigen-antibody reaction in the medium added potassium ion excessively.
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  • Shigetoshi CHIBA, Koroku HASHIMOTO
    1971 Volume 21 Issue 2 Pages 167-173
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In 1955, Burn et al. (1) succeeded in the maintenance of atrial fibrillation by continuous infusion of acetylcholine (ACh) in the dog heart-lung preparation when atrial fibrillation was induced by electric stimulation of auricle. Recently, Hashimoto et al. (2) arranged an adequate method for the selective use of drugs into the sinus node artery in situ by modifying the original preparation developed by James and Nadeau (3), Hashimoto et al. (4) observed that atrial fibrillation was regularly induced by the administration of ACh into the sinus node artery under constant pressure perfusion. They analyzed the mechanism for induction of atrial arrhythmia with ACh, assuming the necessary participation of adrenergic mechanism with essential cholinergic effect of ACh. More recently, Nakayama et al. (5) obtained sustaining atrial fibrillation by continuous infusion of a relatively small amount of ACh directly into the sinus node artery.
    In the present study, the authors observed regularly an occurrence of a sustaining atrial fibrillation by single injection of carbachol, methacholine or bethanechol into the sinus node artery, and compared with the atrial fibrillation induced by ACh.
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  • Sukehiro CHIBA, Yuji NAGAWA
    1971 Volume 21 Issue 2 Pages 175-184
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Nereistoxin is a potent neuroactive substance isolated first by Nitta (1) from the Japanese species of annelid, Lumbriconereis heteropoda Marenz. In our preliminary pharmacological study of synthetic nereistoxin (2), it has been shown in the cat with chronically implanted electrodes that the intraperitoneal injection of 5 mg/kg produced the muscle relaxing signs due to the moderate impairment of the neuromuscular transmission. At the higher dose level than 10 mg/kg, however, this toxin caused salivation, mydriasis, panting, tremor and tonic convulsion which accompanied the spike and dome pattern in electroencephalogram (EEG). Components of this convulsion, tremor and twitching of the limb and body trunk muscles in addition to the EEG seizure patterns were also caused by this toxin in unanesthetized encephale isole cats. This indicates that the sites of the convulsive action of this toxin exist in both the supraspinal and spinal levels.
    The present study was carried out in an attempt to clarify the mechanisms in the spinal cord and at the motor nerve terminal for producing convulsion by nereistoxin. Comparative study of this toxin with the derivatives in the potency was also done.
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  • Yuji NAGAWA, Yoshiaki SAJI, Sukehiro CHIBA, Tohoru YUI
    1971 Volume 21 Issue 2 Pages 185-197
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Chemical and pharmacological studies of a toxin present in Japanese species of a marine annelid, Lumbriconereis heteropoda Marenz, were motivated mainly by the clinical complaints of headache, nausea and respiratory disorder in the fishers using this annelid as a fishing bait. Moreover, it has widely been observed that the feeding of the dead body of this annelid results in the toxic death of carnivorous insects living in seashore.
    Nitta (1-3) first isolated a toxic principle, nereistoxin from the annelid to characterize partly its chemical and pharmacological properties. The chemical structure of nereistoxin clarified by Okaichi and Hashimoto (4, 5) as N, N-dimethylamino-l, 2-dithiolane was quite different from those of the known toxins. Further, their confirmation of powerful insecticidal activity prompted Hagiwara et al. (6) to synthesize nereistoxin and a number of related compounds. One of the derivatives, 1, 3-bis (carbamoylthio)-2-N, N-dimethyl-aminopropane (Cartap, NTD-2) with low toxicity in the experimental animals and with chemical stability has been successfully used as a potent insecticide against the rice stem borer and many of other agricultural pests. The postsynaptic blocking effect of nereistoxin on the central nervous system in the American coakroach was demonstrated by Sakai (7) as the insecticidal mechanism. Furthermore, he showed that nereistoxin had only slight inhibition of cholinesterase activity in housefly's head (8). On the other hand, we have briefly communicated that nereistoxin produces convulsion and blocking of the neuromuscular transmission in mammals (9). This paper deals with the comparison of the neuromuscular blocking effects between nereistoxin and its derivatives, and with the mechanism of neuromuscular block. The neuromuscular blocking effects of nereistoxin and NTD-2 were found to be antagonized by some of sulfhydryl compounds.
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  • Sekizo KOJIMA, Masahiro IKEDA, Akira TSUJIMOTO
    1971 Volume 21 Issue 2 Pages 199-207
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The salivary glands are innervated by both the sympathetic and parasympathetic nerves, receiving a main secretory innervation from the parasympathetic nervous system (1). It was reported that the sympathetic nervous system played an important role in regulation of secretion of amylase, a main component of parotid saliva, from the rabbit parotid gland and that the β receptors were the ones involved in this mechanism (2-5). It is known that catecholamine stimulates adenyl cyclase which may exist in the cell membrane and catalyzes the formation of cyclic AMP in many tissues (6). Robinson et al. (7) postulated that in most and perhaps all tissues the β receptors and adenyl cyclase were probably identical. Bdolah and Shramm (8) reported that theophylline and butyryl derivatives of cyclic AMP induced amylase release from rat parotid slice.
    The present investigation was undertaken to clarify the probable function of cyclic AMP as an inducer of amylase secretion from the rabbit parotid gland in vivo.
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  • Katsumi SUGIYAMA
    1971 Volume 21 Issue 2 Pages 209-226
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has generally been recognized that histamine release from mast cells induced by antigen-antibody reaction, as well as by certain basic compounds, is dependent upon the cellular energy generating processes since these reactions are inhibited by anoxic conditions and by metabolic inhibitors which uncouples oxidative phosphorylation or block respiratory enzymes (1-7). A preliminary study was attempted in order to see whether adenosine 5'-triphosphatase (ATPase) is really activated in association with the release of histamine. However, it was unexpectedly found, at the beginning of such a work, that adenosine 5'-triphosphate (ATP) itself caused a marked histamine release and this was accompanied with conspicuous morphological changes characterized by the degranulation of mast cells when the medium contained calcium ions.
    Keller (8), and Diamant and Krüger (9, 10) have reported that histamine release was elicited by ATP present extracellularly, but the latter authors did not observed the occurrence of degranulation concomitant with the release of histamine even in the calciumcontaining medium, unlike the present observation, although they found some morphological changes in msat cells discernible from those induced by a histamine liberator, compound 48/80.
    The present paper describes observations on the morphological changes and on the release of histamine in isolated rat peritoneal mast cells under the effect of exogenous ATP, with special reference to the combined effect of calcium ions.
    A preliminary report on these findings has been published earlier (11).
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  • Hajime ISHIDA, Naomasa MIKI, Hiroshi YOSHIDA
    1971 Volume 21 Issue 2 Pages 227-238
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The secretion of amines and proteins from glands has been investigated by many workers and it has been suggested that Ca2+ may be important in the secretory process (1-4), but it is uncertain whether Ca2+ actually participates in the secretory mechanism inside the cell.
    The parotid glands are known to be innervated by the sympathetic and parasympathetic nervous systems and acetylcholine and noradrenaline are physiological stimuli that cause secretion of amylase from the gland (5, 6). Amylase is synthesized and stored mainly, in zymogen granules, in the parotid gland (7-10). Ultramicroscopically, zymogen granules are dense, round, osmiophilic bodies of about 1μ diameter, enclosed in a limiting membrane. They are easily isolated from the parotid gland by cell fractionation (8), and are well known to be important in secretion of amylase.
    We study the mechanism of secretion by the parotid glands and the role of Ca2+ in the secretion process, especially in the release of amylase from zymogen granules. A preliminary note on some of this work has already appeared (11).
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  • Hajime ISHIDA, Naomasa MIKI, Fumiaki HATA, Hiroshi YOSHIDA
    1971 Volume 21 Issue 2 Pages 239-251
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In preceding papers (1, 2), we reported that acetylcholine, excess K+ or noradrenaline in the presence of Ca2+ caused secretion of amylase from slices of parotid glands and release of amylase from zymogen granules, consisting mainly of stored amylase. Moreover, ATP and a low concentration of Ca2+ were also important in the process of secretion. Accordingly, there is some secretory process inside the cell which is regulated by Ca2+.
    It has also been reported that the release of catecholamine from chromaffin granules (3-5) and of acetylcholine from synaptic vesicles were caused by ATP (6). Oka et al. (7) also suggested that the release of catecholamine from chromaffin granules is associated with a change in structure of the granules.
    In the present work, we investigated the effect of a low concentration of Ca2+ on the structure of zymogen granules to clarify the relation between release of amylase from the granules and their change in structure.
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  • Norio KURIHARA, Katsuhiro SHIBATA
    1971 Volume 21 Issue 2 Pages 253-261
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In the previous paper on the effects of various chelating agents on the systemic action of Habu snake venom, we reported that the treatment with EDTA enhanced the toxicity of the venom while thiol-compounds such as BAL and d-penicillarnine markedly reduced it (1). In the present work three thiol-compounds, that is 1-cysteine, thioglycolate-Na and dihydrothioctic acid were examined for their effects on the systemic action of Habu snake venom.
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  • Munekazu GEMBA, Juro UEDA
    1971 Volume 21 Issue 2 Pages 263-270
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Since Skou (1) and Post et al. (2) reported, it has been well known that the active transport of ions across the cell membrane is closely related to the (Na+ + K+)-stimulated ATP-ase in the membrane. It is also accepted that mitochondria take up and extrude several kinds of ions from and into the surrounding medium (3-6). Relations between an ion transport and the ATPase activity in mitochondria have been studied by several workers (7-10). Carafoli et al. (8) suggested that ouabain-insensitive ATPase, which was associated with an ion transport, existed probably in the membrane of liver mitochondria. Ozawa et al. (11) reported that the ATPase of brain mitochondria was neither stimulated by sodium and potassium ions nor inhibited by ouabain. In the previous paper, the present authors (12) suggested a participation of ATPase on the ion transport in kidney cortex mitochondria.
    Presently it was tried to make clear the properties of mitochondrial ATPase on ion transport system with special reference to the effects of sodium and potassium ions on enzyme activity.
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  • Keijiro TAKAGI, Issei TAKAYANAGI, Akira TOMIYAMA
    1971 Volume 21 Issue 2 Pages 271-273
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
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  • Toru EGASHIRA, Kazuo TAKANO, Kazunori SHIMIZU, Yasuhiko KUROSAWA, Kazu ...
    1971 Volume 21 Issue 2 Pages 274-276
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
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  • Michio KOJIMA, Takashi NOSE, Keiichi SHINTOMI, Naoto YONEDA
    1971 Volume 21 Issue 2 Pages 276-279
    Published: 1971
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
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  • Takashi BAN, Masakazu HOJO
    1971 Volume 21 Issue 2 Pages 279-282
    Published: 1971
    Released on J-STAGE: February 02, 2007
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