The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 18, Issue 1
Displaying 1-16 of 16 articles from this issue
  • KENJIRO YAMAMOTO, TAKAMICHI HASEGAWA, JURO UEDA
    1968 Volume 18 Issue 1 Pages 1-8
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    In the previous paper (1), the present authors reported a new perfusion method, in which the kidney of a recipient dog with intact innervation was perfused with the donor's blood using an artificial heart-lung apparatus. That method revealed a good response of renal vessels to various vasoactive substances as well as good hemodynamic conditions for about one hour, following by a gradual increase of renal vascular resistance. Such an increase in renal vascular resistance of the perfused dog kidney was also observed by several investigators (2-5), who used perfusion methods somewhat different from the authors' method. But the mechanism for the increase has been left unclarified. In the present study, it was observed that renin was liberated from the perfused kidney, and angiotensin was produced due to interaction of renin and its substrate in the perfusion circuit. The angiotensin thus formed constricted renal vessels, resulting in an increase in renal vascular resistance.
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  • KEIJIRO TAKAGI, SUSUMU OKABE
    1968 Volume 18 Issue 1 Pages 9-18
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    Various procedures have been reported on the biossay of antiulcer drugs . Pylorus ligation of the rat (1-3), restraint of the rat (4, 5), water immersion of the restrained rat (7) and the application of ulcerogenic agents on various animals (8-11) were used for producing experimental ulcers. In these methods the drug had been administered to the animal before the ulcer production and the preventive effect on the ulcer producing processes was tested. Although some drugs such as glutamine or methylmethionine sulfonium chloride were recently introduced to promote the repair of the ulcer which had existed already, suitable methods are lacking for their pharmacological test, and so it was hoped to develop a new method for pharmacological assay of curative activity of the drugs on existing ulcers. In the present paper curative effects of some drugs on the stress ulcer of the rat are reported.
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  • YOOKO TOHYA, SADAYO SASAGAWA
    1968 Volume 18 Issue 1 Pages 19-29
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    The retarding effect of the orally administered acidic protease (TE-P), isolated from Trametes sanguinea, on the spontaneous delivery in the pregnant rats but not in the pregnant rabbits has been reported by Shimamoto (1). Though exact nature of the retarding mechanism is still unknown, the enzyme is assumed to be absorbed from the gastrointestinal tract without loosing the proteolytic activity and to exert the interfering with the delivery process in virtue of some pharmacological effects of the proteolytic products of the tissue or plasma. This indication was further supported by the evidence that the in vitro incubation of the commercial globulin with the adequate concentrations of TE-P at the acidic reaction produced the pharmacologically active substance unique in evoking a slow contraction of the smooth muscle (2). The present authors have also confirmed that the similar incubation of the homogenates of the rat spleen, kidney and liver with the enzyme resulted in the formation of the active substance, which definitely differs pharmacologically from acetylcholine, histamine, 5-hydroxytryptamine and bradykinin. Moreover, it has been confirmed that the incubation of the tissue homogenates alone at the acidic reaction produces another active substance, which contracts the isolated rat uterus, retarded in onset and slow in progress. In the present experiments, efforts were made to separate pharmacologically and biochemically both active substances in order to know the pharmacological properties of the proteolytic substance in the incubation of the liver homogenates with TE-P.
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  • SHUNKICHI TAMURA, SHOJI TSUTSUMI, HIROO ITO, KAZUHITO NAKAI, MICHIO MA ...
    1968 Volume 18 Issue 1 Pages 30-38
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    It has been generally recognized that in a living body various biochemical changes were induced as a consequence of hard physical exercise. In the previous paper (1), the authors reported on the metabolism of glucuronic acid in the case of fatigue by physical exercise. This report was summarized as follows: the toxic (amine-like) substance in a living body increased due to physical exercise, and resulted in fatigue. The glucuronic acid content of urine, serum, liver and kidney, and the hepatic glycogen content of a living body decreased. The activity of o-aminophenylglucuronide synthesis of rat's liver was inhibited after hard physical exercise. However, these phenomena were significantly blocked by the administration of glucuronolactone. The arrest of an isolated frog heart due to the accumulation of toxic substance was checked, both prophylactically and therapeutically, by the administration of glucuronolactone. Dutton et al. (2-8) have recently proved that glucuronic acid exerted its effect after it was converted into uridine-diphospho-glucuronic acid. It is therefore apparent that exogenous glucuronic acid cannot exert its effect unless it is changed into uridine-diphospho-glucuronic acid through the Xylulose pathway, or different pathway not yet known. Though the authors have no description of the mechanism of these pathway at present, it is a fact that glucuronolactone can inhibit the toxic substance which stopped the beating of a frog's heart. As well known, uridine-diphospho-glucuronic acid is converted from various kinds of carbohydrate, namely glucose, galactose, glycogen and sodium pyruvate. The authors therefore proceeded to ascertain the effects of these carbohydrates and glucuronolactone upon the swimming-record, o-aminophenylglucuronide synthesis, glucuronic acid content, ascorbic acid content, blood sugar content, hepatic glycogen content, and β-D-glucuronide glucuronohydolase activity in albino rats made to swim hard.
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  • IWAO YAMAMOTO, HIROSHI KIMURA, KATSUYA IWATSUBO
    1968 Volume 18 Issue 1 Pages 39-47
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Since 1953 we have studied the specific toxicogenic mechanism of various nitrogen mustard derivatives (1-10). As described by Philips (11), Goodman and Gilman (12) and Yamamoto et al. (4, 6), the toxicity of nitrogen mustards can be broadly classified into acute and delayed cytotoxic actions, both of which are extremely specific. Because of the toxicity of these drugs there is consequently a clinical restriction in the dosage. However, as these nitrogen mustard derivatives show a significant morphological effect on experimental cancer, extensive basic and clinical studies are still being continued on these compounds to search more excellent cancer chemotherapy. In the present study methyl-bis (β-chloroethyl) amine N-oxide hydrochloride (nitromin) was selected and investigations were directed to reduce its toxicity. Data obtained demonstrated that the pretreatment with reserpine inhibited the lethality of nitromin and thus further studies were made on its inhibition mechanism with relation to biogenic amines.
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  • J.N. SINHA, K.S. DIXIT, R.C. SRIMAL, K.P. BHARGAVA
    1968 Volume 18 Issue 1 Pages 48-53
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    Tricyclic antidepressants like imipramine (IMI), desmethylimipramine (DMI) and amitriptyline (AMI) have been shown to antagonise muscle rigidity in experimental reserpine depressive syndrome (1-4) as well as in clinical depressive states. Imipramine also abolishes the rigidity associated with parkinsonism (5). We have earlier reported that these agents possess a potent central muscle relaxant activity of longer duration (6-8). Orphenadrine another structurally similar antidepressant has been reported to possess both central and peripheral muscle relaxant activity (9-11). Chlorpromazine, a tranquillizer causes skeletal muscle re l a xation in certain spastic disorders. Both supraspinal (12) and spinal (13) components have been reported for such activity. Preferential blockade of monosynaptic reflexes has been reported for major tranquillizers (14). Chlorpromazine has been shown to have less potent antistrychnine activity than mephenesin. Bhargava and Srivastava (15) also reported that chlorpromazine is less potent than mephenesin in antagonizing strychnine induced potentiation of linguomandibular polysynaptic reflex. Like tricyclic antidepressants, MAO inhibitors also antagonize reserpine induced muscular rigidity. However, no report regarding the central muscle relaxant activity of these agents is available in the literature. The commonly employed group of drugs in the treatment of psychic disorders are antidepressants, tranquillizers and stimulants. We have earlier suggested that the central muscle relaxant activity of imipramine and allied drugs, plays an important role in their antidepressant action. The present study was undertaken with two aims; firstly to find out a potent central muscle relaxant of longer duration than mephenesin secondly to explore the role of such an inhibitory activity (central muscle relaxant activity) in the antidepressive, tranquillizing and stimulant action of the drugs.
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  • II. A PARTICIPATION OF CATECHOLAMINE IN THE ANTAGONISM
    HIROSHI TAKAGI, MOTOTAKA NAKAMA
    1968 Volume 18 Issue 1 Pages 54-58
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Ealier observations in this laboratory have demonstrated that tetrabenazine, a brain monoamine releaser, antagonizes morphine analgesia in mice (1) and that it antagonizes the depressive effects of morphine on the several afferent pathways in the central nervous system in cat (2). More recently it has also been demonstrated that the change of brain noradrenaline (NA) plays more important role than that of serotonin (5-HT) in the antagonism of morphine analgesia by tetrabenazine or reserpine (3) and that morphine decreases the content of dopamine (DA) as well as that of NA in the brain (4). The purpose of this study was to investigate the mechanism of tetrabenazine antagonism of morphine analgesia in relation to DA and NA content in the brain.
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  • I. A POSSIBLE PARTICIPATION OF PROTEOLYTIC ENZYME IN PLASMA
    HIROSHI TAKAGI, ISAMI KURUMA, YASUYUKI NOMURA
    1968 Volume 18 Issue 1 Pages 59-67
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Recently it was shown by Kuruma et al. (1) and Takagi and Kuruma (2) that a single injection of bacterial pyrogenic lipopolysaccharide (LPS) into rabbit caused a marked reduction of 5-hydroxytryptamine (5-HT) content in brain stem and spleen, without affecting on the content of noradrenaline and the time course of 5-HT decrease in brain stem is closely correspond with that of rise in rectal temperature. This observation prompted us to study the mechanism of 5-HT release induced by LPS using platelet since it has been shown that the use of platelets is a valuable experimental procedure for study of the 5-HT release mechanism (3). Although 5-HT releasing effect of LPS on platelet has been reported previously by Shimamoto et al. (4, 5), Des Prez (6-8) and Davis el al. (9, 10), its mechanism is remains to be investigated.
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  • II. COMPARISON OF MORPHOLOGICAL CHANGES IN PLATELETS INDUCED BY VARIOUS RELEASERS
    ISAMI KURUMA, HIROSHI TAKAGI
    1968 Volume 18 Issue 1 Pages 68-79
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Previous works in this laboratory (1, 2) have demonstrated that bacterial pyrogenic lipopolysaccharide (LPS) caused a decrease in 5-hydroxytryptamine (5-HT) content of rabbit brain and spleen. Furthermore, it was also shown that LPS induces 5-HT release from rabbit platelet only in the presence of Ca ion and plasma component which is destroyed at 56°C (3). The present report describes morphological studies on the effect of several 5-HT releasers, including LPS, on the rabbit platelets in vitro.
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  • SHINSAKU KOBAYASHI, HIROMU TAKAGI
    1968 Volume 18 Issue 1 Pages 80-85
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    It is well known that the parenteral use of bacterial pyrogen produces fever reaction in men, dogs, cats and rabbits. From the practical reason of easier management, rabbits have been widely used for pyrogen test as well as for screening of the antipyretic activity of different kinds of compounds. But it is a big advantage if the smaller animals can be used for screening of antipyretic agents. Recently, Winter et al. (1) and Yamada et al. (2) reported a marked rise of rectal temperature of rats with one or two hours latency, when bacterial lipopolysaccharide was used as pyrogen. Based on this finding, Winter et al. adapted this response to the screening of antipyretic agents. In the authors' laboratory, any detectable fever response by bacterial lipopolysaccharide is not obtained in rats, while the definite pyretic effect of a bacterial lipopolysaccharide and typhoid-paratyphoid vaccine is observed in guinea pigs. Moreover, antipyretic effect of different structure of compound is successfully screened in fevered guinea pigs.
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  • G. ACHARI, C.N. SINHA
    1968 Volume 18 Issue 1 Pages 86-88
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    Dimethyl sulfoxide (DMSO) was first prepared by Alexander Saylzeff in 1866 and is now obtained from waste product in paper manufacture. Though primarily used as an unusual solvent, the chance discovery of its skin penetrability triggered off series of investigations about the clinical usefulness of the agent and its various biological actions (1). In light of the forementioned work, it was considered worthwhile to investigate the action of DMSO on Finkleman preparation of rabbit ileum.
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  • TETSUO SATOH, TAKIO IWAMOTO
    1968 Volume 18 Issue 1 Pages 89-92
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    The preceding paper (1) revealed that electroshock induced the elevation of blood serotonin level which caused the changes of carbohydrate metabolism, i.e., hypoglycemia, hyperlactacidemia, decrease of liver glycogen and disappearance of initial peak in glucose tolerance test in rats. Recent investigation by Frieden et al. (2) has indicated the inhibition of tryptophan pyrrolase (TPO) activity by serotonin and indole derivatives in vitro. In the present study we have therefore investigated the changes of both liver serotonin level induced by electroshock or administration of monoamine oxidase inhibitor (MAOI) and TPO activity.
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  • YASUO ISHII, HARUHIKO SHINOZAKI
    1968 Volume 18 Issue 1 Pages 93-103
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    The antral hormones, gastrin I and II were isolated in pure form from hog antral mucosa by Gregory and Tracy (1). Gregory et al. (2) showed that the gastrins were polypeptides containing 17 amino acids and their structures were subsequently confirmed by total synthesis by Anderson et al. (3). During the studies on synthetic polypeptides structurally related to gastrin, Tracy and Gregory (4) discovered that the C-terminal tetrapeptide, Try. Met. Asp. Phe. NH2, could show the full range of physiological actions of natural porcine gastrin, even though it was quantitatively less active. The gastric secretory actions of gastrin-like peptides have been investigated in anesthetized rats by Barrett (5), and Barrett et al. (6), in conscious or anesthetized dogs by Morley et al. (7), Konturek and Grossman (8), on the isolated gastric mucosa of the bullfrog by Davidson et al. (9), and in clinical investigations by Wormsley et al. (10), Makhlouf et al. (11), Konturek (12) and Fitzgerald (13). They described that gastrin-like peptides were the specific gastric secretory stimulants which possessed the properties necessary to replace histamine in assessing the maximal acid response of patients and were usefull as the new tool for research in gastric secretion. Recently, we gained a new acylated derivative of tetrapeptide amide, t-amyloxycarbonyl Try. Met. Asp. Phe. NH2 (14). The present study is concerned in the comparison of this tetrapeptide with other secretagogues such as other gastrin-like peptides, histamine, bethanechol etc. using various preparations of rats and in other pharmacological studies of several gastrin-like peptides.
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  • AKITOSHI SHIOYA, IWAO OHISHI, MORIO KAKIMOTO
    1968 Volume 18 Issue 1 Pages 104-112
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    In a previous paper (1), the authors demonstrated that changes in serum β-glucuronidase activity paralleled blood sugar levels after the administration of glucose, epinephrine and insulin, while an inverse relationship was found with hydrocortisone treatment. Furthermore, we observed that the changes in serum β-acetylglucosaminase activity in such cases were somewhat different from that of β-glucuronidase. On the other hand, several investigators (2-7) have shown an increase in serum β-glucuronidase activity of diabetic patients. Among them, however, only Woolen and Turner (6) has observed a significant correlation between plasma β-glucuronidase activity and blood sugar levels. In the present study we have extended our survey of the relationship between serum β-glucuronidase activity and the blood sugar level in experimental diabetic rabbits, prepared by a single injection of alloxan or consecutive administrarion of hydrocortisone.
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  • MOTOHATSU FUJIWARA, KEISUKE HATTORI, HIDEO MIZUSAWA, TAKASHI MURYOBAYA ...
    1968 Volume 18 Issue 1 Pages 113-129
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
    JOURNAL FREE ACCESS
    Octopamine (p-hydroxy-β-phenylethanolamine) was first extracted from the salivary glands of octopus (1). Later it was found in human and animal urine (2). More recently, it has been isolated and identified from extracts of juice and leaves of Meyer lemon (3). The conversion of tyramine to octopamine has been shown in vitro by a broken cell preparatoin (4) and by isolated organs (5). Octopamine has also been found in the salivary glands, heart and spleen of rats after tyramine administration (6-9). Lemberger and associates have presented evidence that an appreciable portion of tyramine is converted to octopamine in vitro (10). Octopamine is capable of replacing noradrenaline in its storage sites and the octopamine is released by sympathetic nerve stimulation. Thus, octopamine is proposed as a false neurochemical transmitter (8, 9). Since Lands and Grant (11) first evaluated a pressor action of octopamine, several reports have appeared regarding the pharmacological action of octopamine, and this compound has long been used as a pressor agent in hypotensive patients. However, no detailed report on the pharmacological effects of octopamine in reference to the biochemical conversion to noradrenaline is available. In the present experiments it was attempted to correlate sympathomimetic effects of octopamine with the endogenous noradrenaline by means of pharmacological, biochemical and histochemical techniques.
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  • II. ULCEROGENIC ACTIVITIES OF RESERPINE AND ITS ANALOGUES
    MASAMI DOTEUCHI
    1968 Volume 18 Issue 1 Pages 130-138
    Published: March 01, 1968
    Released on J-STAGE: February 02, 2007
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    The mechanism of ulcer formation by reserpine has been studied by many investigators. Recently, it was demonstrated that even a small dose of reserpine could produce considerably severe ulcers when combined with stress such as restraint (1), conflict (2), electrical stimulation of the hypothalamus (3, 4) and electrical shock through a grid in the floor (4). Concerning the site of action of reserpine, Blackman et al. (5) have described that reserpine-like drugs cause gastric hemorrhage by a mechanism which has an important central component and which involves the liberation of serotonin. On the other hand, Nicoloff et al. (6) reported that norepinephrine administered into the gastric artery provoked ulceration when active acid secretion was present. From these findings it may be considered that ulcers could be produced by peripheral as well as central mechanisms. The author (7) has previously shown that a decrease in serotonin contained in the enterochromaffin cell and norepinephrine contained in vasoconstrictive nerve endings caused by reserpine and stress had close correlation with ulcer formation. In the present paper differences in the ulcerogenic activities between reserpine and its analogues combined with electrical shock through a grid on the floor were investigated. Reserpine analogues used in this study involved two types of drugs, those that release peripheral monoamines and those that release central monoamines.
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