The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 22, Issue 2
Displaying 1-21 of 21 articles from this issue
  • Yasuo ISHII, Rinzo NISHIZAWA, Shigeru MIZUGUCHI, Hiroshi MIYAZAKI
    1972 Volume 22 Issue 2 Pages 139-146
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The antral hormone, gastrin, is a linear polypeptide with seventeen amino-acid residues. Since Tracy and Gregory (1) elucidated that the C-terminal tetrapeptide amide, Trp.Met.Asp.Phe.NH2 produces all the physiological effects of the entire molecule, C-terminal tetrapeptide and pentapeptide amides instead of gastrin have been used for investigation of gastric acid secretion and diagnosis of gastric function. There have been numerous reports concerning pharmacological effects of gastrin and these peptides, very little, however, is known about their metabolism.
    The present study is an attempt to investigate the difference in distribution, absorption and excretion of exogenous gastrin and gastrin-like tetrapeptide using iodine-125 labeled gastrin and tritiated tetrapeptide while making a comparison of their biological activities.
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  • I. PRODUCTION OF RABBIT ANTIBODIES AGAINST RAT GASTRIC MUCOSA AND GASTRIC JUICE
    Koichiro KAWASHIMA, Keijiro TAKAGI
    1972 Volume 22 Issue 2 Pages 147-153
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    It has been shown that rabbits injected with a homogenate of rat gut mucosa produce auto-antibodies reacting with their own gut mucosa (1). Hausamen et al. (2) have demonstrated that the injection of an aqueous extract of guinea pig stomach into rabbits leads to the production of hetero- and auto-antibodies against parietal cell antigen, gastric intrinsic factor and mucous substances confined to the stomach. Hennes et al. (3) reported that antibodies, reacting with gastric juice and an extract of dog gastric mucosa, were found in dogs immunized with gastric juice from various sources. This paper describes the production of gastric antibodies to rat gastric antigens by the injection of rat gastric mucosa and gastric juice into rabbits, and characterization of these antibodies.
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  • II. EFFECTS OF RABBIT ANTIBODIES AGAINST RAT GASTRIC MUCOSA AND GASTRIC JUICE, ON GASTRIC SECRETION IN THE RAT
    Koichiro KAWASHIMA
    1972 Volume 22 Issue 2 Pages 155-165
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The etiology of atrophic gastritis has not been established. Although the circulating antibody to a constituent of the gastric parietal cell has been demonstrated in a large number of patients with pernicious anemia and atrophic gastritis (1-5), the significance of the parietal cell antibody in causing or perpetuating any type of chronic gastritis is unknown. Jacob and Glass (6) have presented direct evidence that the parietal cell antibody is a complement fixing antibody, and have supported the concept that the autoimmune mechanism participates in the development of the gastric atrophic lesion in a proportion of patients with pernicious anemia and atrophic gastritis. Fiasse et al. (7) failed to show inhibition of gastric secretion after a single injection of human parietal cell antibody in the rat. On the other hand, Tanaka and Glass (8) have reported that rats injected with human parietal cell antibody for 6 to 8 weeks showed a profound decrease of hydrochloric acid output, and had mild atrophic lesions in the gastric mucosa. Hausamen et al. (9) have shown that the injection of rabbit antisera against antigens from guinea pig gastric mucosa into guinea pigs, resulted in an acute inflammation confined to the stomach. In the present study, shortand long-term effects of rabbit antibodies against rat gastric mucosa and gastric juice on gastric secretion in the rat, were investigated.
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  • Yoshikazu NAKAZATO, Akira OHGA
    1972 Volume 22 Issue 2 Pages 167-174
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    It is well known that reserpine causes a depletion of catecholamine and 5-hydroxytryptamine contents in various organs and tissues thereby preventing sympathetic transmission (1, 2). In order to eliminate sympathetic effects on gastro-intestinal motility, reserpine has usually been given to animals for a few days or at least 20 hr before experiment (3-5). One disadvantage of these experiments is that observation of a control response to stimulation of the sympathetic nerve cannot be done.
    Recently it has been observed that reserpine added to bathing solution was effective in reducing or abolishing the sympathetically induced response of isolated preparations (6-8). In these experiments, it has been presumed that mechanisms other than an overall depletion of catecholamine contents possibly accounted for the acute inhibitory action of reserpine.
    The present experiment was made to elucidate whether or not an acute effect of reserpine can be demonstrated on the sympathetically induced response of the dog stomach in vivo. Theresult showed that a single large dose of reserpine injected intravenously inhibited selectively the sympathetic nerve response within 4-5 hr.
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  • K.C. SINGHAL, OM CHANDRA, P.N. SAXENA
    1972 Volume 22 Issue 2 Pages 175-179
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Setaria cervi (1, 2), a cosmopolitan nematode parasite of cattle, lives in the peritoneal cavity. 85% of cattle are found infected with Setaria cervi. The maximum number of worms (60 to 70 in each head) is found between mid June to August after which the number declines and from December to January incidence is as low as 10 to 20 Setaria cervi per head. From February onwards the number starts increasing. The ratio of male and female Setaria cervi in cattles has been found to be 1 : 1.21, but incidence of infection in these animals is very low. Setaria cervi has been found to be more common in goats and sheep and Setaria cervi in horses. No report is however available regarding the incidence of infection by Setaria cervi in neighbouring countries. Little is known about the life history and mode of transmission, but a blood sucking arthopod vector is presumed to be involved in the completion of the life cycle. Williams (3) succeeded in transplanting these worms from freshly slaughtered cattle to rabbits and showed the presence of microfilariae in the peripheral circulation of the rabbits. Although Williams (3) did not succeed in finding an arthopod vector, his results indicated the possibility of keeping the nematodes alive in an experimental host. Later, Nelson (4) succeeded in transplanting both adult worms and microfilariae to rabbits and monkeys. The morphology of the adult worm and microfilaria is described by Ansari (5). Adult worms measure 10.0±2.5 cm (male) and 15.0±2.0 cm (female) in length. The microfilariae are microscopic structures 277±14.0 μ long and 7.5±1.5 μ wide. Ansari (6) successfully implanted the adult worms intraperitoneally in rats and studied microfilariae periods in the peripheral circulation. Maximum density of the microfilariae in the peripheral blood occurred between 6-8 a.m. and 6-8 p.m. Singhal et al. (7) also successfully transplanted the adult worms of Setaria cervi intraperitoneally in rats and reported disappearance of microfilariae from the peripheral circulation after oral administration of diethylcarbamazine. In the present study an attempt has been made to extend these observations and to establish the value of Setaria cervi as a test organism for the screening of antifilarial agents.
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  • Hiroshi KOGO, Yoshio AIZAWA
    1972 Volume 22 Issue 2 Pages 181-186
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In 1961, one of the authors (1) demonstrated that estrogen stimulated the biosynthesis of phospholipids in the ovariectomized rat uterus and phospholipid metabolism constitutes an unusually sensitive indicator of early estrogen action. Recently, Roskoski and Steiner reported that estrogen injection increases the initial rate of 3-0-methylglucose transport into uterine cells and this transport takes place by means of a specific mobile carrier transport system (2).
    Phospholipid is an essential component of biological membrane (3, 4) and it has been clarified that phospholipid affects various enzymic reactions (5-10). Membrane lipid is also of interest in this regard as it may play an important role in transport of a substance through cell membrane.
    This present report is an investigation as to whether or not sugar transport into uterine cells, which is accelerated by estrogen administration, is affected by phospholipids in vitro. It was observed that sugar transport in the spayed rat uterus increased with the addition of phospholipid.
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  • Kiyomi SAEKI, Saburo MURAOKA, Hidemasa YAMASAKI
    1972 Volume 22 Issue 2 Pages 187-199
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    It has been known that a variety of non-steroidal anti-inflammatory drugs uncouple oxidative phosphorylation in mitochondria (1-5). Adams and Cobb (2) have studied whether or not the inhibition of inflammation by non-steroidal drugs was related to their in vitro capacity to uncouple oxidative phosphorylation. Whitehouse (6) has made an extensive survey on this problem.
    We have reported that a variety of non-steroidal anti-inflammatory drugs inhibit the degranulation of isolated mast cells of the rat, which is blocked by uncouplers of oxidative phosphorylation as well as by inhibitors of the respiratory chain (7). It was then found that anti-inflammatory activity of these drugs bore quantitative relation to their in vitro capacity to inhibit the degranulation. In addition, anti-inflammatory effect of 2, 4-dinitrophenol, dicoumarol and warfarin was also demonstrated. These results appear to favor the hypothesis proposed by Whitehouse (6) that the uncoupling activity of non-steroidal anti-inflammatory drugs may be causally related to their inhibitory effect on inflammation.
    Flufenamic acid [N-(3-trifluoromethylphenyl) anthranilic acid; Fig. 1, R1=H, R2=CF3] and mefenamic acid [N-(2, 3-dimethylphenyl) anthranilic acid; Fig. 1, R1=CH3, R2=CH3] have proven to have potent anti-inflammatory activities and are being applied to clinical uses (8-10). If the above hypothesis is acceptable, antiinflammatory activities of a series of N-phenylanthranilic acid (PAA) derivatives, including these two drugs, may be reflected by their relative activities in uncoupling oxidative phosphorylation. The present experiment was undertaken to determine whether or not a correlation exists between the uncoupling potencies of PAA derivatives on oxidative phosphorylation in rat liver mitochondria and their anti-inflammatory activities on the carrageenin edema in rat paws. Some physicochemical properties of the compounds were also examined.
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  • Takaaki FUJII, Hideo NISHIMURA
    1972 Volume 22 Issue 2 Pages 201-206
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Teratogenic and embryocidal actions of adenine in the mouse were demonstrated (1-2). Since adenine is an important purine metabolite in animals of all kinds as well as in plants, it was decided to investigate other purine metabolites and a xanthine oxidase inhibitor as to whether or not similar actions on developing mouse embryos could he demonstrated.
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  • Motoo OKA, Futoshi IZUMI, Takeshi KASHIMOTO
    1972 Volume 22 Issue 2 Pages 207-214
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    There is evidence that Ca++ is required for the release of catecholamine from the adrenal medulla evoked by acetylcholine or a high K+ concentration (1, 2) and that an increased influx of Ca++ into the cell occurs during this process (3). It has therefore been proposed that it is the entry of Ca++ into the cell which somehow triggers the secretory process (4, 5). On the other hand, the release of catecholamine from isolated catecholamine storage granules is shown to be stimulated by ATP and Mg++ (6-8) and this ATP-Mg++ stimulated release of catecholamine also requires a low concentration of Ca++ (<10-5M), present as a contaminant in the reaction mixture (9). The authors suggested that ATP-Mg++ stimulated release of catecholamine from the granules could be a step in the secretory response of the adrenal medulla.
    To elucidate the exact intracellular mechanism of adrenal medullary secretion, it is necessary to determine whether or not intracellular elements other than catecholamine storage granules are involved in the regulation of catecholamine release from the granules. We have investigated the effects of the cytoplasmic and microsomal fractions on ATP-Mg++ stimulated catecholamine release from the granules. Results suggest that these two fractions are important in regulation of catecholamine release from the adrenal medulla.
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  • Koichi NAKAYAMA, Norio TAIRA, Koroku HASHIMOTO, Shinsaku KOBAYASHI, Se ...
    1972 Volume 22 Issue 2 Pages 215-220
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Anisotropine methylbromide (A.M.; Valpin®) is a tropine ester related structurally to atropine and homatropine methylbromide, and has been synthesized by Gordon and Weiner (1). The chemical name is 2-propylpentanoyl tropinium methylbromide and structural formula is as shown in Fig. 1.
    In previous experiments, Taira et al. (2) found that the vocalization response of dogs to acetylcholine (Ach) administered into a branch of the mesenteric artery was selectively abolished by atropine. On the other hand, sodium salicylate was also found to be effective for prevention of the vocalization response to Ach, although a larger dose was needed in the mesenteric artery than in the femoral. They concluded that the vigorous contraction of the intestine through a muscarinic mechanism probably plays an important role in the induction of the nociceptive response, although possible involvement of other mechanisms cannot be ruled out. In the present experiments the analgetic effect of A.M. and of its mixture with sulpyrine was assessed, the procedure being essentially the same as described by Taira et al. (2) and Nakayama et al. (3).
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  • Suehiro NAKANISHI, Eiko SHIOHARA, Miyoko TSUKADA, Go KINOSHITA
    1972 Volume 22 Issue 2 Pages 221-225
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    During the past fifteen years, it has become evident that a variety of lipid soluble drugs such as aniline, aminopyrine and hexobarbital are oxidized by NADPH-dependent enzymes in hepatic microsomes (1-4). Cytochrome(s) P-450 plays a critical role as the terminal oxidase in the metabolism of drugs, steroids and heme (5-7). It is generally accepted that the hepatic drug-metabolizing enzyme system has few specificities for substrates but recent studies have suggested the existence of more than two microsomal enzymes which metabolize the drugs (8, 9).
    On the other hand, the addition of various substrates of microsomal mixed-function oxidase system to aerobic liver microsomes causes two types of spectral change. One class of spectral change (termed type I) is characterized by the appearance of a trough at 420 mμ and an absorption peak at 385 mμ. Aminopyrine, hexobarbital, chlorpromazine, SKF 525-A and DDT cause type I spectral change. Another class of spectral change (termed type II) is characterized by the appearance of a trough at 392 mμ and an absorption peak at 430 mμ. Aniline, nicotinamide, pyridine and p-aminophenol cause type II spectral change (10).
    Drug interaction with endoplasmic reticulum occurs not only to constitute enzymesubstrate complex but also to modify the physical properties, amounts, composition and turnover of constitutive membrane components (11). At present aniline is thought to bind to the CO-binding site of cytochrome P-450, whereas aminopyrine or hexobarbital is thought to bind to the lipids of the endoplasmic reticulum or hydrophobic region cytochrome P-450 (12).
    The present paper concerns the effects of type I binders such as aminopyrine, hexobarbital and chlorpromazine on p-hydroxylation of aniline in vitro.
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  • Mitsuyoshi NAKASHIMA, Yasumichi HAGINO
    1972 Volume 22 Issue 2 Pages 227-233
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    It has been generally accepted that only beta adrenergic receptors are present in myocardial tissue, however, there are many reports of the existence of both alpha and beta receptors in mammal's hearts (1-4). In our laboratory also, existence of alpha adrenergic receptors was certified in rat atria (5): dose response curve of positive inotropic action of phenylephrine (PHE) shifted to the left after 6-propyl-2-thiouracil (PTU) treatment and depressed profoundly by phentolamine.
    In chronotropic response, alpha receptors have been minimally implicated. James et at. (6) reported that in dogs, methoxamine's negative chronotropic action is due to alpha receptor stimulation.
    The present paper concerns changes of sensitivity in positive chronotropic response to PHE and to isoproterenol. (ISO) after PTU treatment and adrenalectomy. Involvement of alpha adrenergic receptors in chronotropic response to PHE in rat atria are discussed.
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  • Takashi OCHIAI, Yoshio KOWA, Kentaro OKUMURA
    1972 Volume 22 Issue 2 Pages 235-244
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In 1959, R. Charlier reported that the most potent choleretic action was found in p-hydroxyphenyl salicylamide (Driol, PHPS) among the derivatives of benzoic acid (1). Moreover, G. Bonola et al. reported that 1-morpholinoacetyl-3-phenyl-4-oxo-1, 2, 3, 4, -tetrahydro quinazoline (Moquizone, MQZ) has the most potent choleretic activity among their derivatives (2, 3). Recently, many derivatives of 1-aminoacetyl-2-alkyl-3-phenyl-4-oxo-1, 2, 3, 4-tetrahydro quinazoline, which include basically the main structure of PHPS and MQZ, have been synthesized by K. Okumura et al. (4, 5). From the relationship between the chemical structure and the choleretic activity, it was found that 1-morpholinoacetyl-2-methyl-3-phenyl-4-oxo-1, 2, 3, 4-tetrahydro quinazoline (hereafter referred to as HQ-275) has the most potent choleretic activity among these derivatives. In the present experiment, qualitative evaluation of the choleretic activities of quinazoline derivatives were carried out mainly in rats. As the choledochal bile of rat devoid of gall bladder, is qualitatively and quantitatively expression of the hepatic bile, it has a constitution very similar to that of humans. In addition to the choleretic action, other pharmacological studies and toxicity of HQ-275 were also compared with those of dehydrocholic acid (DHC), PHPS, α-(1-hydroxy-cyclohexyl)-butylic acid (HCHB) and p-tolylmethyl-carbinol (PTMC) in rabbits, cats and dogs.
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  • Keijiro TAKAGI, Hiroshi SAITO, Hiroyuki NABATA
    1972 Volume 22 Issue 2 Pages 245-259
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Ginseng root has been utilized for thousands of years in China, Korea and Japan as an important drug in Chinese medicine. Chemical researches on Ginseng root have been reported by a number of investigators (1-8), especially Shibata and his co-workers have investigated the chemical structure of Japan-cultivate-Panax gieseng saponins and sapogenins (9-16).
    Several papers concerning the extracts of Ginseng root have been reported in the pharmacological fields (17-21). Petkov (22-24) reported the stimulant effects of Ginseng root on the central nervous system, the respiration and the adrenal cortex. It was reported that Ginseng root stimulates gastric and intestinal motility (25), corrects nutritional disorders (26) and depresses mean arterial blood pressure (27). Wood et al. (28) investigated the effect of Ginseng root on cardiovascular system in the dog.
    It is very difficult and costly to study systematically detailed pharmacological effects of oriental plants. In our laboratory, a systematic analysis of pharmacological properties of a chemical compound have been studied (29). This analytical method was appliedto the study of Ginseng root saponins.
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  • N.K. KHANNA, P. PANDHI
    1972 Volume 22 Issue 2 Pages 261-262
    Published: 1972
    Released on J-STAGE: December 19, 2006
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  • N.K. KHANNA, R.S. GUPTA, A.K. MATHUR, K. GUPTA
    1972 Volume 22 Issue 2 Pages 262-264
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • REPORT 1. DEPRESSANT ACTION ON EEG AROUSAL RESPONSE INDUCED BY DIFFERENT SENSORY STIMULATIONS
    Hiroshi KUROMI, Masamichi SATOH, Hiroshi TAKAGI
    1972 Volume 22 Issue 2 Pages 264-266
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Go KINOSHITA, Eiko SHIOHARA, Miyoko TSUKADA, Riichiro MASUMURA, Suehir ...
    1972 Volume 22 Issue 2 Pages 267-269
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Hironori NAKANISHI, Hiroshi TAKEDA
    1972 Volume 22 Issue 2 Pages 269-270
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Wen-Hsiung LEE, Motohatsu FUJIWARA
    1972 Volume 22 Issue 2 Pages 271-273
    Published: 1972
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Shigetoshi CHIBA, Koroku HASHIMOTO
    1972 Volume 22 Issue 2 Pages 273-274
    Published: 1972
    Released on J-STAGE: December 19, 2006
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