Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 91, Issue 4
Displaying 1-10 of 10 articles from this issue
  • Den'etsu SUTOO, Kayo AKIYAMA, Ichiro MAEDA
    1988 Volume 91 Issue 4 Pages 173-180
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    A new fluorescence microphotometry system was developed for analysis of the distributions and amounts of neurotransmitter and its related chemical substances in the smaller brain regions. This system can measure fluorescence intensity of 10, 000 points in animal brain slices which were immunohistochemically and histochemically stained. This system mounts a photomultiplier tube of high sensitivity and high linearity to a detector; therefore, this system surpasses in quantitative capability by two figures compared with an image analyzer which uses a high-sensitivity TV camera. The high-precision step-motor scanning stage moves under the objective lens of the fluorescence microscope and analyzes the entire surface of the slice: measuring speed, 250 points/min; maximum measuring area, 76 × 52 mm. The data of fluorescence intensity and position (X and Y value) on the slice are transmitted to a computer, calculated statistically and displayed two- and three-dimensionally. In this study, immunohistochemical distribution and intensity of acetylcholine, choline acetyltransferase and acetylcholinesterase in the rat cervical spinal cord were measured. The distributions of their chemical substances are consistent with previous observations. This system is applicable to a wide range of neuroscience studies.
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  • Masao SAKURAI, Isamu KOMINE, Nobutaka DEMURA, Takashi SAKAGUCHI, Masay ...
    1988 Volume 91 Issue 4 Pages 181-186
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The CNS effects of propentofylline and caffeine, methylxanthine derivatives, were compared. In mice, caffeine antagonized diazepam-induced muscle relaxation and the inhibitory effect of diazepam against pentylenetetrazole-induced convulsions, but propentofylline did not. In spinal cats, the dorsal root reflex potentials were inhibited by caffeine but not affected by propentofylline, and the monosynaptic reflex potentials were increased by propentofylline but not influenced by caffeine. The results indicate that propentofylline differs from caffeine in that it neither antagonizes diazepam nor affects the GABA system.
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  • Rie WATANABE
    1988 Volume 91 Issue 4 Pages 187-196
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The author reports that a relatively high dose of verapamil produces sex-related cardiac effects, especially on the conducting system in adult rats. A single dose of verapamil (0.5-1 mg/kg, i.v.) caused a marked AV block and a reduction in heart rate to 50-60% in adult males, but not in females. There was no sex difference in the hypotensive effect of verapamil. At 3, 5 or 7 weeks of age, verapamil (1 mg/kg, i.v.) induced a 10-20% reduction of the heart rate without AV block in both male and female rats. In 8-week-old male rats, the reduction in the heart rate became apparent, and AV block appeared following a single i.v. injection of verapamil. The adult pattern in cardiac response to verapamil was observed at 11 weeks of age and afterward. Castration in adult male and female rats resulted in an intermediate pattern of the response to verapamil in intact male and female rats. Acute treatment with testosterone (20 mg/kg, s.c.) in castrated male and female rats induced a decrease in the basal heart rate and increased the cardiac responsiveness to verapamil in castrated female rats. Estradiol-17β failed to alter the responsiveness of castrated rats to verapamil. These results suggest that testosterone may play a role in the sex difference of the cardiac responses to verapamil in rats.
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  • Satoru OZAKI, Isao OHKAWA, Yoshinori KATOH, Tetsuya TAJIMA, Masaichi K ...
    1988 Volume 91 Issue 4 Pages 197-207
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    Experiments were performed to investigate the effects of mecobalamin (CH3-B12) on disorders of testicular function. Male rats received subcutaneously an injection of doxorubicin (ADR) three times a week for 3, 5 and 7 weeks. Thereafter, they were periodically sacrificed for the examination of cauda epididymal sperm profiles and the morphology of the testis. ADR treatment caused a decrease in sperm counts, sperm motility and the diameter of the seminiferous tubules, and an increase in the percentage of abnormal sperms. These damaging effects depended on the dosage and period of treatment with ADR. Based on these findings, rats with testicular dysfunction induced by the treatment with ADR at a daily dose of 0.25 mg/kg, three times a week for 5 weeks were prepared to investigate the effects of CH3-B12 on oligozoospermia. CH3-B12 was given intraperitoneally to the oligozoospermic rats six times a week for 5 and 10 weeks. The results obtained indicated that 1, 000 μg/kg of CH3-B12 caused a significant increase in both the sperm counts and the diameter of the seminiferous tubules. These results suggest that CH3-B12 is a candidate drug for oligozoospermia.
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  • Tsukao NISHIMORI, Kyuya MORINO, Michio TSUCHIYAMA, Hironobu IKEDA, Kao ...
    1988 Volume 91 Issue 4 Pages 209-220
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The effect of cadralazine, a new antihypertensive agent, were studied on the central nervous systems in experimental animals. Oral administration of 0.5 mg/kg or more of cadralazine depressed spontaneous motor activity and enhanced electroshock-induced convulsions in mice. The drug produced flush on the tail or ears at 0.5 mg/kg, p.o. or more and enhanced respiratory movement at 5.0 mg/kg, p.o. or more in rats. At 2.5 mg/kg, p.o., cadralazine prolonged the thiopental-sleeping time and inhibited methamphetamine-induced hypermotility as well as acetic acid-induced writhing in mice. Pretreatment of naloxone, however, failed to antagonize this inhibitory effect on acetic acid-induced writhing. Cadralazine at 5.0 mg/kg, p.o., lowered body temperature in rats. This same dose antagonized tremorine-induced behaviors in mice. Cadralazine at a dose of 1.0 or 5.0 mg/ kg, i.v., had no effect on the spontaneous EEG pattern and the threshold of arousal EEG response induced by electrical stimulation to the midbrain reticular formation in rabbits. Even at a dose as large as 100 mg/kg, p.o., the drug showed no significant effect on the following effects : conditioned avoidance response in rats, spinal reflex in cats, tail pinch-induced pain in mice, and somatic function in the inclined screen or in the traction test in mice. In conclusion, cadralazine, having no passage through the blood-brain barrier, showed several pharmacological actions on behaviors. These actions are considered to be derived from its vasodilative properties and were qualitatively similar to those of hydralazine.
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  • Tsukao NISHIMORI, Takaharu NISHIMURA, Fumio KOBAYASHI, Daizaburo NAKAN ...
    1988 Volume 91 Issue 4 Pages 221-236
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The general pharmacological effects of cadralazine and its major metabolite ISF 2405 were studied by comparing them with those of hydralazine. Cadralazine at 3.0 mg/kg, i.v., increased respiratory movement and heart rate and decreased blood pressure in cats. Cadralazine at 3.0 mg/kg, i.v., inhibited the hypertensive response induced by adrenaline, but showed little effect on the hypotensive response induced by acetylcholine in cats. Cadralazine and ISF 2405 at 10-4 g/ml had negative chronotropic effects on isolated guinea-pig atria. The drug at 2.5 mg/kg, p.o., inhibited the passage of BaSO4 in the gastrointestinal tract in mice. The drug at 5.0 mg/kg, i.d. or more inhibited gastric secretion in rats. Cadralazine, except at higher doses, had little effect on spontaneous gastric motility and uterine spontaneous movement in rats. Cadralazine at 2.5 mg/kg, p.o., or more reduced or tended to reduce urine volume and urinary excretion of electrolytes. The drug showed little effect on coagulation and osmotic fragility in blood cell in rats nor on hemolysis and platelet aggregation in rabbits. ISF 2405, however, showed slight or moderate influence on hemolysis at concentrations as high as 0.01 ?? 1.0%. Cadralazine at 5.0 mg/kg, p.o. or more antagonized carrageenin-induced hind paw edema in rats. In conclusion, these effects of cadralazine were found to be qualitatively identical with those of hydralazine.
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  • Shigefumi TAKEDA, Ichiro ARAI, Masayuki HASEGAWA, Akemi TATSUGI, Masak ...
    1988 Volume 91 Issue 4 Pages 237-244
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    TJN-101 ((+)-(6S, 7S, R-biar)-5, 6, 7, 8-tetrahydro-1, 2, 3, 12-tetramethoxy-6, 7-dimethyl-10, 11-methylenedioxy-6-dibenzo [a, c] cyclooctenol) is one of the lignan compounds isolated from Schisandra fruits. When TJN-101 was administered orally at the doses of 3-100 mg/kg/ day for 4 days, bile secretion, hepatic excretion of dye or hepatic hemodynamics 24 hr after the last dose was investigated in comparison with the phenobarbital (100 mg/kg/day)-treated group. Bile flow was dose-dependently increased; in contrast, biliary concentration of bile acids was decreased in TJN-101 (30 and 100 mg/kg/day)-treated groups. Similar changes were also observed in the phenobarbital-treated group. These results suggested that the enhancement of bile secretion caused by TJN-101 or phenobarbital was due to an increase of a bile acid-independent fraction. In the bromosulfophthalein (BSP) clearance test for liver function, both TJN-101 (30 and 100 mg/kg/day) and phenobarbital accelerated the disappearance from the blood and biliary excretion of BSP. Hepatic hemodynamics was examined by the hydrogen clearance method and measurement of liver wet and dry weight. Liver blood flow tended to increase in the TJN-101 (10-100 mg/kg/day) or phenobarbitaltreated group. On the other hand, TJN-101 (3-100 mg/kg/day) or phenobarbital hardly altered the water content of the liver. These results suggested that the liver enlargement caused by both compounds was not accompanied with hepatic edema and that the enhancement of bile secretion or hepatic excretion of BSP might be related to an increase of liver blood flow.
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  • Chiyoji OHKUBO
    1988 Volume 91 Issue 4 Pages 245-253
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    Effects of acetylcholine (ACh) and its reversed carboxy analogue, methyl N-trimethyl-γ-aminobutyrate chloride (MTB), induced either by topical application to the skin surface around a transparent round table chamber (REC) that had been previously installed to the ear lobe or by intravenous injection on the micro- and macrocirculations were studied in the healthy male rabbit. The effects of both drugs on the cutaneous microcirculation within the REC were observed vital-microscopically under conscious conditions and the microcirculatory events were visualized with a microscope-closed TV system and microphotoelectric plethysmography. The results were as follows : (1) Topical application of 1 % MTB cream caused an enhanced perfusion of rhythmic microvascular blood due to vasomotion for a period of 30 min or longer, while ACh did so to a much less extent, if any. On the other hand, no appreciable change developed in any systemic hemodynamic parameters. (2) Intravenous administration of MTB or ACh caused a very transient dilator effect on micro- and macrocirculatory blood vessels according to its cholinergic stimulation, which could be blocked by atropinization. Almost the same efficacy on vasomotion was observed for each drug. (3) These findings indicate that the topical application of MTB to the skin surface may cause a physiologically acceptable vasodilation accompanied by vasomotion, and it would facilitate the oxygen diffusion by the follicular circulation.
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  • Masahiro MIZOTA, Yukio KATSUKI, Kiyoshi MIZUGUCHI, Shoji ENDO, Haruo M ...
    1988 Volume 91 Issue 4 Pages 255-266
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The effects of eicosapentaenoic acid ethylester (EPA-E) at daily doses of 3 and 30 mg/kg (p.o.) on vascular lesions and changes in blood components were investigated in rabbits fed with a 1 % cholesterol diet for 12 weeks and partly compared with those given 30 mg/kg/ day (p.o.) of ticlopidine. EPA-E at 30 mg/kg significantly improved the reduction in distensibility of isolated thoracic aorta caused by cholesterol diet feeding. Ticlopidine at 30 mg/kg also showed significant but milder improvement. EPA-E at 30 mg/kg, unlike ticlopidine, tended to lower cholesterol content in the thoracic wall and elastin fraction. Although EPA-E did not act on plasma total cholesterol, HDL-cholesterol and triglyceride contents, it tended to mildly reduce platelet aggregability in response to sodium arachidonate and the increased production of TXA2-like activity by platelets. In addition, daily doses of 30 mg/kg EPA-E caused a significant increase in plasma and platelet EPA-E contents without any change in docosahexaenoic acid and arachidonic acid contents. From these results, daily administration of EPA-E to cholesterol diet-fed rabbits caused a remarkable improvement of the reduction in distensibility of isolated thoracic aorta. The mechanism of this improvement by EPA-E appears to depend on the protection of elastic fibers from lipid deposition on the vascular wall.
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  • Satoshi TAKEO, Kouichi TANONAKA, Tomoyuki HIRANO, Keiko MIYAKE, Junko ...
    1988 Volume 91 Issue 4 Pages 267-273
    Published: 1988
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The present study was designed to elucidate whether naftidrofuryl oxalate (LS-121) may exert a beneficial effect on survival time and cerebral energy metabolism of bilateral carotid artery (BCA)-ligated mice. Survival time of BCA-ligated mice ranged from 100 to 308 sec. Administration of 15, 45 and 100 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 significantly prolonged the survival time. Cerebral adenosine triphosphate (ATP), creatine phosphate (CP) and glucose contents were markedly reduced at 2 min after BCA-ligation. Cerebral lactate content was increased by the ligation, whereas the pyruvate content was not altered. Pretreatment of mice with 15, 45 mg/kg, i.p. and 100 mg/kg, p.o. LS-121 suppressed BCA-ligation induced decrease in high-energy phosphates of the mouse brain. Ligation-induced decrease in glucose and increase in lactate content tended to be attenuated by the treatment with 45 mg/kg, i.p. LS-121. Time course of changes in metabolic variables altered by BCA-ligation with and without the pretreatment with 45 mg/kg, i.p. LS-121 showed a significant suppression of ligation-induced decrease in cerebral high-energy phosphates. The results suggest that LS-121 is beneficial for ischemic mouse brain energy metabolism, which may be related to the prolongation of the survival time.
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