The Japanese Journal of Pharmacology
Online ISSN : 1347-3506
Print ISSN : 0021-5198
ISSN-L : 0021-5198
Volume 30, Issue 4
Displaying 1-22 of 22 articles from this issue
  • Issei TAKAYANAGI, Akira KARASAWA, Yutaka KASUYA
    1980 Volume 30 Issue 4 Pages 405-412
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of nonspecific smooth muscle relaxants, an uncoupler and removal of Ca ions from physiological solution on the tissue concentrations of high energy phosphates, such as ATP and creatine phosphate (CP) and tension of the normal polarized and KCl-depolarized intestinal smooth muscles of guinea pig were studied. Decrease of CP-concentration induced by dinitrophenol (DNP; 10-4 M) was accompanied by relaxation of the normal polarized and KCl-depolarized smooth muscles. DNP slightly (but significantly) decreased ATP-concentration in the normal polarized and KCl-depolarized smooth muscles. Application of papaverine (3×10-5 M) relaxed the normal polarized taenia immediately but increased CP-concentration at 5 and 10 min and decreased the concentration at 20 min. When the depolarized smooth muscle was considerably relaxed by papaverine (3×10-5 M), there was little influence on the CP-concentration. After relaxation of the depolarized taenia as induced by papaverine had reached a maximal amplitude, CP-concentration decreased significantly. ATP-concentration was little influenced by papaverine in the normal polarized and KCl-depolarized muscles. Although the treatments with a synthetic antispasmodic drug, Aspaminol (3×10-4 M), which was found to inhibit Ca-uptake by the intestinal smooth muscles, a Ca-blocker, D-600 (10-6 M) and removal of Ca ions from physiological solution relaxed the polarized and depolarized smooth muscles, the tissue concentrations of CP and ATP increased. These phenomena are considered to be due to decrease of the intracellular Ca-concentration.
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  • Shizuka HIGASHI, Yoshio AIZAWA
    1980 Volume 30 Issue 4 Pages 413-419
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effect of gonadotropins and ovarian hormones on adrenal estrogens in female rats was examined in relation to the ovarian function. Pregnant mare serum gonadotropin (PMS) increased adrenal estradiol level in intact rats but did not alter estrone levels. Human chorionic gonadotropin (HCG) with PMS did not alter the estrone and estradiol levels. Neither PMS or HCG with PMS affected these steroid levels in ovariectomized rats. Injection of hexestrol to intact rats decreased the estrone level. Further decrease in the estrone level resulted after administration of hexestrol with progesterone. In a developmental study, the estrone level at 35 days of age was higher than that at 50 and 80 days of age. The estrone level gradually decreased with adrenal development after ovariectomy performed at 21 days of age. When adrenal slices were incubated with either 3H-estrone or 3H-estradiol, higher radioactivity of estrone accumulated in the adrenal gland of immature rats than in that of adult rats. There was a larger conversion of 3H-estradiol to 3H-estrone than the reverse process in both immature and adult rats. These results indicate that the adrenal estrogens were influenced by ovarian function.
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  • Akie KOJIMA, Sumie KAWANO, Kogo HIRAGA
    1980 Volume 30 Issue 4 Pages 421-426
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Hepatic 9, 000×g supernatant (S9) fraction from 3-methylcholanthrene (MC)-treated rats showed a significantly low activity in the in vitro conversion of 2-acetylaminofluorene (AAF) to mutagen(s), while S9 fraction from untreated or phenobarbital (PB)-treated rats showed a remarkable activity. The S9 fraction from MC-treated rats actually suppressed the PB-S9 mediated AAF mutagenicity. Since the suppressive effect of MC-S9 was lost by the addition of 10-4 M α-naphthoflavone (α-NF), rat specific cytochrome P-448 may be responsible for this suppressive effect.
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  • Katsuji HOSHI, Sumiko FUJINO
    1980 Volume 30 Issue 4 Pages 427-435
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    To further clarify the hypotensive mechanism of adrenergic alpha blockers, effects of several alpha blockers on systemic blood pressure and on Ca-contracture of isolated, cat aortic strips were studied. For this purpose, the effects of known adrenergic alpha blockers, phentolamine, phenoxybenzamine, and a newly synthesized adrenergic alpha blocker (2-(N-(n-Butyloyl)homopiperazine-N'-yl)-4-amino-6, 7-dimethoxy quinazoline; E-643) were compared with those of nitroglycerin and verapamil. Systemic blood pressure was decreased by administration (2×10-8 moles/kg i.v.) of all drugs except phenoxybenzamine. The order of maximal fall of diastolic blood pressure after the injection was; nitroglycerin>E-643>phentolamine>verapamil>phenoxy-benzamine. Although “adrenaline reversal” was observed after 2×10-7 moles/kg of phenoxybenzamine, i.e. a 10-fold increase in the dose of phenoxybenzamine, there was no decrease in systemic blood pressure with this dose. All these drugs in a concentration of 2×10-6 M inhibited the Ca-contracture (phasic and tonic) of the depolarized aortic strips. The order of inhibition of phasic and tonic contracture was: nitroglycerin> E-643, verapamil>phentolamine>phenoxybenzamine. The pA2 values for phentol-amine and E-643 in antagonizing contractions produced by noradrenaline of cat aortic strips were 7.8 and 8.2, respectively. Hypotensive effects of these drugs (except phenoxy-benzamine), paralleled the inhibitory effects on the Ca-contracture of the aortic strips. These results suggest that alpha blockers such as phentolamine and E-643 exert a systemic hypotensive effect not through their alpha blocking action but by an inhibitory action on the contractile Ca-mechanism.
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  • Akihide KODA, Kenichi SAKAMOTO, Yukiyoshi YANAGIHARA
    1980 Volume 30 Issue 4 Pages 437-447
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A study was conducted to examine the effect on homologous PCA in rats of 14 different, newly synthesized compounds, given orally, in relation to the chemical structure of DSCG, when given orally on homologous PCA in rats. The structure-activity relationship of these compounds was also discussed. Among the 7 compounds of the glycerol bischromenonyl ether derivatives, 1, 3-bis (2-phenyl-4-chromenon-5-yl) oxypropane-2-ol (compound 1) showed the most potent inhibitory activity on PCA. The other compounds showed a moderate or no effect. Two compounds of glycerol bisphenyl ether derivatives had little effect. On the other hand, 1, 3-bis (2-carboxy-3-hydroxyphenyl)oxypropane (compound 11) out of alkandiol bisphenyl ether derivatives significantly inhibited PCA, and the other 4 compounds showed a tendency toward inhibition of the reaction. The late inhibition, seen in the biphasic inhibitory pattern induced by compound 11, may be caused by a certain active substance transformed in the body.
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  • Norio TAIRA, Yutaka IMAI, Masao HIWATARI
    1980 Volume 30 Issue 4 Pages 449-461
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    To obtain detailed information concerning the effects of different vasodilators on venous return, experiments were carried out on 28 dogs by the use of the open-loop method. Blood from the superior and inferior venae cavae was drained at the level of the tricuspid valve into a reservoir, from which blood was pumped into the right atrium at a constant flow rate. Changes in reservoir volume reflected a total blood shift from the experimental dog and indicated changes in venous return. Drugs were administered into the ascending aorta. Nitroglycerin (1-10 μg/kg) decreased systemic blood pressure, total peripheral resistance and venous return but scarcely altered heart rate. Trimetazidine (0.3-3 mg/kg) decreased systemic blood pressure, total peripheral resistance, venous return and heart rate. Verapamil (10-100 μg/kg) decreased systemic blood pressure, total peripheral resistance and heart rate, and increased venous return. SK&F 24260 (1-10 μg/kg) decreased systemic blood pressure, total peripheral resistance and increased venous return. Only high doses (10-30 μg/kg) of SK&F 24260 reduced heart rate. Rigorous measurements of systemic output showed that nitroglycerin (10 μg/kg), trimetazidine (3 mg/kg), verapamil (100 μg/kg), SK&F 24260 (10 μg/kg) produced no change in this parameter. SK&F 24260 increased venous return even when sino-aortic baroreceptor reflex was eliminated, ruling out reflex venoconstriction as a possible cause of the increased venous return. The results suggest the following: [1] Vasodilators like SK&F 24260 and verapamil increase venous return by decreasing arterial and/or venous resistance. [2] If the effect which increases venous capacitance prevails over the effect which decreases arterial and/or venous resistance, venous return is reduced as is the case of nitroglycerin and trimetazidine.
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  • Toshiji MIYAGAWA, Shinobu SAKURADA, Keisetu SHIMA, Ryuichiro ANDO, Nor ...
    1980 Volume 30 Issue 4 Pages 463-469
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of intravenously administered morphine on the evoked potentials of the amygdala elicited by tooth pulp stimulation were examined in cats. The various evoked potentials were observed in regions of the amygdala such as nucleus amygdaloideus centralis (pars lateralis), nucleus amygdaloideus basalis (pars magnocellularis), nucleus amygdaloideus basalis (pars parvocellularis) and nucleus amygdaloideus lateralis. Evoked potentials were significantly decreased by morphine in four of the recorded regions. Morphine had no effect on the latency at any site of the amygdala observed. Depressant effects of morphine on evoked potentials were antagonized by naloxone in all 14 cats. This study indicates that there is a receptive field of pain in the amygdala which undoubtedly plays a role in emotion.
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  • Mikio ITO, Tadashi NAGAMATSU, Yoshio SUZUKI
    1980 Volume 30 Issue 4 Pages 471-479
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Using a modified model of Masugi's nephritis of rats, various enzymatic activities in urine, serum and renal tissue (glomeruli or cortex) were determined at appropriate intervals after the administration of anti-kidney serum and compared with the urinary protein content and the kidney weight. In the urine, alkaline phosphatase (Al-Phosase), acid phosphatase (Ac-Phosase) and N-acetyl-β-glucosaminidase (NA-β-Gase) activities remarkably increased after the induction of nephritis, reached their peaks on the 10th day and reverted to almost the normal levels on the 30th day. The patterns of time course of these enzymatic activities were similar to patterns seen in the urinary protein content and the kidney weight. In the serum, the Al-Phosase activity decreased slightly, while NA-β-Gase activity increased slightly. The AcPhosase activity in serum remained at normal levels during the experimental periods. In the glomeruli, the bound activities of these three enzymes decreased with nephritis, showing a negative correlation with results in the urine. On the other hand, fibrinolytic activities in the urine (plasmin-like enzyme) and renal cortex (plasminogen activator) also paralleled the urinary protein content and the kidney weight in the course of the disease. These results suggest that the Al-Phosase, Ac-Phosase and NA-β-Gase excreted into urine in cases of nephritis may be mostly derived from damaged renal cells and one part of Al-Phosase may also come from the plasma. Moreover, the increase of plasmin-like enzyme in urine is considered to be due to the increase of plasminogen activator in the renal cortex. Thus, the determination of these enzymatic activities in the urine should be useful for evaluating effects of drugs for the treatment of nephritis.
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  • Che-Hui KUO, Hiroshi YOSHIDA
    1980 Volume 30 Issue 4 Pages 481-492
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The ACh-releasing factor, which is required for ACh release in presence of 2 mM ATP, 2 mM Mg and 10-5 M Ca from isolated synaptic vesicles, was purified from the synaptosomal cytoplasm of rat brain by Sephadex G-15, DEAE-Sephadex, Sephadex G-10 and AG50W-2X column chromatographies and identified as ascorbic acid. A low concentration of L-ascorbic acid (5×10-6 M) produced a release of ACh from the vesicles in the presence of ATP, MgCl2 and CaCl2, as did synaptosomal cytoplasm. This release of ACh induced by L-ascorbic acid was found to be dissociable from formation of lipid peroxide. These findings are discussed in relation to the physiological role of L-ascorbic acid in the brain.
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  • Hiromu KAWASAKI, Shigenori WATANABE, Ryozo OISHI, Showa UEKI
    1980 Volume 30 Issue 4 Pages 493-502
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of delta-9-tetrahydrocannabinol (Δ9-THC) on the cardiovascular system, and pressor and behavioral responses to brain stimulation were investigated in rats. In urethane-anesthetized rats, intravenous administration of Δ9-THC (1, 2 and 5 mg/kg) produced a significant and transient dose-related rise but no fall in blood pressure. Δ9-THC at these doses also produced marked reduction in heart rate which was antagonized by atropine (0.5 mg/kg i.v.) or bilateral vagotomy. In freely moving rats with chronically implanted electrodes and arterial cannula implants, intraperitoneal administration of Δ9-THC (4, 6 and 8 mg/kg) induced a rise in blood pressure and marked bradycardia. Abnormal behavior such as catalepsy, walking backwards and pivoting was also observed. Δ9-THC failed to inhibit the pressor responses to electrical stimulation of the posterior hypothalamus and midbrain reticular formation, whereas the drug suppressed the behavioral responses to stimulation of both regions. It is concluded that the cardiovascular effects seen with Δ9-THC injection are mainly the result of alteration of the efferent vagal activity by acting on the central nervous system and a more potent influence is exerted on the behavioral changes than on autonomic responses to brain stimulation.
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  • Mamoru SUGIURA, Hiroyuki OHNO, Masahiro KUNIHISA, Fumio HIRATA, Hitosh ...
    1980 Volume 30 Issue 4 Pages 503-513
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    A water-soluble polysaccharide, D-II with marked antitumor activity was isolated from the cultured mycelium of Coriolus versicolor by extraction with hot-water, fractional precipitation with ethanol and ion-exchange chromatography. D-II strongly inhibited the growth of Sarcoma-180 transplanted subcutaneously in mice by intraperitoneal, intravenous, subcutaneous or intra-muscular administration at a dose of 5 mg/kg. The molecular weight was estimated to be 2, 000, 000 by gel-filtration or 6, 500, 000 by light scattering analysis. The chemical structure of D-II was then investigated by periodate oxidation, methylation analysis, Smith degradation, and a combination of controlled Smith degradation and methylation analysis. These studies proposed that D-II is composed of a unit structure of four D-glucose residues, and is a glucan consisting of β-D-1, 3-linked main chain in which one for every three D-glucose residues is branched at C-6 with β-D-1, 6-linkage.
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  • Susumu SATOH, Susumu FUJISAWA, Reiko TANAKA, Kengo NAKAI
    1980 Volume 30 Issue 4 Pages 515-519
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effects of captopril administered intravenously in a dose of 1 mg/kg on systemic blood pressure (SBP), renal blood flow (RBF) and renal vascular resistance (RVR) were examined in pentobarbital anesthetized dogs. Untreated dogs were used in experiments in which the renal artery remained intact and others in which the renal artery was partially occluded (RAO). Captopril significantly decreased SBP, increased RBF and decreased RVR in untreated dogs. RAO induced an increase in arterial plasma renin activity and this increase was accompanied by an increase in RVR in the contralateral kidney and rise in SBP. During RAO, captopril induced qualitatively similar, but greater decreases in SBP and RVR of the contralateral kidney compared with those in the untreated dogs. These results suggest the vasodilator effect of captopril depends on the background level of angiotensin II and the enhanced effect would be expected under conditions such as RAO where circulating angiotensin II contributes to vascular tone.
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  • Yasumichi HAGINO, Toshihiko UEMATSU, Masakatsu TACHIBANA, Hiromichi TS ...
    1980 Volume 30 Issue 4 Pages 521-528
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The effect of thyroid hormone on the activity of low Km cyclic AMP phosphodiesterase of the particulate fraction from the kidney was investigated. This enzyme activity increased in the cortex from hypothyroid rats and reverted to the normal level after the subcutaneous administration of L-3, 5, 3'-triiodothyronine (T3) daily for 3 days. However, this hormone did not affect the enzymes from the normal rats. In vitro experiments revealed that T3 as well as various known phosphodiesterase inhibitors similarly inhibited the activity of low Km cyclic AMP phosphodiesterase from both normal and hypothyroid rat kidneys. The results of the present study suggest that the effect of thyroid hormone on cyclic AMP phosphodiesterase was not direct but was mediated by a modulation of the rate of protein synthesis and an unknown mechanism in the kidney.
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  • Michiko INOUE, Masako MORIKAWA, Minoru TSUBOI, Yoshimasa ITO, Mamoru S ...
    1980 Volume 30 Issue 4 Pages 529-535
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    In attempts to determine the exact role of intestinal esterase in the body, we purified esterases from human intestinal mucosa and liver, and compared the enzymatic properties and substrate specificities with those of purified esterases. Esterase from human liver was purified 58-fold, by treatment with butanol, DE-52 and DEAE Sephadex A-50 column chromatographies, Sephadex G-200 gel filtration, and isoelectric focusing. The purified preparation showed a single band by polyacylamide gel electrophoresis. The molecular weights of intestinal and hepatic esterases were determined to be 53, 000-55, 000 and 180, 000, respectively, by gel filtration on Sephadex G-200. The activity of the purified intestinal and hepatic esterases was strongly inhibited by diethyl-p-nitrophenyl phosphate and diisopropyl fluorophosphate, and was not inhibited by eserine sulfate and p-chloromercuribenzoate. Moreover, the purified esterases hydrolyzed ester-type drugs such as aspirin, clofibrate, indanyl carbenicillin and procaine. Hepatic esterase had properties similar to those of intestinal esterase with respect to the sensitivity to organophosphate and the substrate specificity. However, the two purified esterases differed in properties such as molecular weight, isoelectric point, thermostability and optimal pH.
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  • Kazuhiro GOTO, Michio TERASAWA, Yukinobu KADOBE, Yutaka MARUYAMA
    1980 Volume 30 Issue 4 Pages 537-547
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    The active anaphylactic bronchoconstriction of rats mediated by IgE-like antibody against DNP-Ascaris was inhibited by intravenous and intratracheal treatment with Y-12, 141 in a dose-dependent manner. In both routes, the inhibitory effect of Y-12, 141 on this response was more potent than that of disodium cromoglycate (DSCG). The oral administration of Y-12, 141 also produced a similar inhibition of the response. The passive anaphylactic bronchoconstriction of guinea pigs mediated by IgG-like antibody against egg albumin was also prevented dose-dependently by treatment with Y-12, 141 given intravenously, but not with DSCG. The present results suggest that Y-12, 141 may be effective for the treatment of allergic bronchial asthma.
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  • Yoshiteru HARADA, Kunio TANAKA, Makoto KATORI
    1980 Volume 30 Issue 4 Pages 549-557
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
    Effects of MK-447 on prostaglandin (PG) endoperoxide formation from arachidonic acid by bovine seminal vesicle microsomes in the presence of cofactors (hemoglobin and tryptophan) were studied by cascade superfusion on rabbit aorta and mesenteric artery and rat stomach and colon. In the presence of hemoglobin (0.2 μM), MK-447 (up to 30 μM) accelerated PG endoperoxide formation, as tryptophan did, whereas higher concentrations of MK-447 lost the acceleration effect and finally inhibited the PG endoperoxide formation. Increased concentration of hemoglobin (2 μM) shifted the dose of MK-447 for peak generation from 30 to 100 μM. Thus, MK-447 shows dual action, acceleration and inhibition, on the PG endoperoxide formation.
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  • Akihide KODA, Kenichi SAKAMOTO, Kunihiro NAKAMURA, Tetsuyuki KANO
    1980 Volume 30 Issue 4 Pages 559-561
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Shigetoshi CHIBA, Yasuyuki FURUKAWA, Miyoharu KOBAYASHI
    1980 Volume 30 Issue 4 Pages 562-565
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Hiroko MURAKAMI, Tomio SEGAWA
    1980 Volume 30 Issue 4 Pages 565-567
    Published: 1980
    Released on J-STAGE: December 19, 2006
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  • Akira NISHIO, Seizaburo KANOH
    1980 Volume 30 Issue 4 Pages 568-570
    Published: 1980
    Released on J-STAGE: December 19, 2006
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  • Fumiaki HATA, Shuji UCHIDA, Kunio TAKEYASU, Hajime ISHIDA, Hiroshi YOS ...
    1980 Volume 30 Issue 4 Pages 570-574
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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  • Masao KOIDA, Hiromichi NAKAMUTA, Shinichi FURUKAWA, Ronald C. ORLOWSKI
    1980 Volume 30 Issue 4 Pages 575-577
    Published: 1980
    Released on J-STAGE: December 19, 2006
    JOURNAL FREE ACCESS
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