Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 77, Issue 4
Displaying 1-10 of 10 articles from this issue
  • Izuru MATSUOKA
    1981 Volume 77 Issue 4 Pages 337-346
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    The paper deals with recent advances in anatomical, physiological, biochemical and pharmacological studies on the vestibular system. Fiber connections and characteristics of neurons in the vestibular nuclei were discussed in relation to regulation from other structures such as the cerebellum, oculomotor nuclei, reticular formation and spinal cord. In addition, a review was made of the actions on the vestibular system of antivertigo drugs including anticholinergic and antihistamine drugs, tranquilizers and barbiturates. All the obtained data show that the vestibular nuclei are devoid of noradrenergic, dopaminergic and serotonergic innervation, in contrast to other brainstem nuclei. Acetylcholine is apparently a neurotransmitter in the afferent transmission from the vestibular nerve to the vestibular nuclei. Antivertigo drugs produce modification in the neuron activity in the medial and lateral vestibular nuclei.
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  • Takao SHIMIZU
    1981 Volume 77 Issue 4 Pages 347-360
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Effects of peripheral electric stimulation (PES) on the functional state of central 5-hydroxytryptamine (5-HT) and on the analgesic effect were investigated in mice. The PES was administered by a passing rectangular wave (0.45 mA, 5 msec, 5 ?? 100 Hz) for 2 hr through bipolar electrodes implanted subcutaneously at the base of the tail. Whole brain 5-HT concentration remained unchanged with the PES at 20 Hz, whereas 5-hydroxyindoleacetic acid concentrations were significantly increased in the whole brain. A significant increase in the whole brain compared with that in control was already attained at 30 min after initiation of the PES. Number of head-twitches induced by 5-methoxy-N, N-dimethyltryptamine after the PES was clearly potentiated. Increase in the number of head-twitches after the PES was abolished by administration of p-chlorophenylalanine, a 5-HT depletor, and 5, 6-dihydroxytryptamine, a 5-HT neurotoxin. The PES for I hr produced an antinociceptive effect. Administration of L-5-hydroxytryptophan enhanced the antinociceptive effect induced by PES, while methysergide and naloxone completely abolished this antinociception. Thus, 5-HT neurons are probably excited functionally by the PES, and the mechanisms of analgesia produced by the PES involve both endogenous opiate systems and central serotonergic mechanisms.
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  • Hiroyuki KOHNO, Tsukasa SAKURADA, Kensuke KISARA, Hiroko SATOH
    1981 Volume 77 Issue 4 Pages 361-370
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    The intraperitoneal administration of spermine (SPM) produced a dual-phasic feeding suppression. The first suppression appeared immediately after the administration and disappeared on the 2nd day. The next suppression was observed on the 3rd day and continued for 2-4 days. The 50% dose which induced suppression on the 3rd day was 64.9(60.9-69.2) μmol/kg. Drinking behavior was also suppressed on the 1st day, but was facilitated on the 2nd day and lasted for 4-5 days. Serum gulcose and free fatty acids concentrations increased after the administration of SPM (80 μmol/kg). Their maximal values obtained at 3 hours after the dosing were 116% and 156% of the control values, respectively. These increases in both substances were not observed in the adrenal-demedullated rats. The same dose of SPM enhanced serum glutamic oxaloacetic transaminase and glutamic pyruvic transaminase activities. The maximal values obtained at 2 hours after the dosing were 264% and 142% of the control values, respectively. On the contrary, serum cholinesterase activity decreased to 44% of the control value at the same hour. These variations of the enzyme activities disappeared at 3 hour, but were again observed between the 1st and 4th days. These results suggest that SPM releases catecholamines from the adrenal medulla, and exerts a toxic action on the liver. The anorexia induced by SPM may be due to these actions on the viscera.
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  • Kiyomitsu KAMEI
    1981 Volume 77 Issue 4 Pages 371-381
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Since the use of nitroglycerin (NTG) in cases of acute myocardial infarction is controversial, the effects of this drug were studied using experimental animals. NTG was given to open chest dogs during induced acute ischemia and the motion and the wall thickness of left ventricle were examined using the method of Gaasch and Bernard. Mongrel dogs weighing 10 to 25kg (average 15kg) were anesthesized with urethane, α-chloralose and morphine. A mini-transducer was immobilized on the surface of left ventricular wall and the motion and thickness of left ventricular wall were measured by Ultrasound. In some dogs, an electromagnetic flowmeter probe was attached to the left anterior desending coronary artery and the coronary blood flow and aortic pressure were measured. One of diagonal branches was then ligated, acutely. After a steady state had been reached, 30 γ/kg or 100 γ/kg of NTG was administered intravenously and changes in the wall thickness were measured serially. After this ligation, the wall thickness decreased rapidly and reached a plateau 90-120 min after. Following administration of 30 γ/kg and 100 γ/kg of NTG, both end-systolic wall thickness and maximal rate of wall thickness during systole were restored, the former 12.7±2.2 to 13.7±2.0 mm and 12.5±2.5 to 13.9±2.5 mm (p<0.05 in both), the latter from 37.0±16.7 to 55.0±26.5 mm/sec and 41.0±27.8 to 56.0±33.7 mm/sec (p<0.001 in both). Concomitant with these effects were a transient increase in coronary blood flow and a decrease in aortic pressure. These observations indicate that abnormal wall motion and performance of the left ventricle are improved with NTG administration, thus this drug should be clinically effective for treating patients with acute myocardial infarction.
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  • Takeru KANEKO, Satoru OZAKI, Kiyomi YAMATSU
    1981 Volume 77 Issue 4 Pages 383-395
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Flunitrazepam in a dose range of 0.01 to 1 mg/kg i.v. produced dose dependent sedation and muscle relaxation, while even 1 mg/kg of flunitrazepam had no anesthetic effect (loss of righting reflex). Flunitrazepam in a dose over 0.01 mg/kg prolonged anesthesia induced by pentobarbital, thiopental and ketamine in mice and rats and combinations of non-effective doses of these anesthetics with flunitrazepam induced anesthesia in mice. Furthermore, flunitrazepam enhanced gaseous anesthesia in mice and rats. Flunitrazepam alone was slightly effective in prevention of acetic acid writhing in mice and the drug enhanced the anti-writhing effects of morphine, pentazocine and thalamonal. Flunitrazepam alone had little analgesic effect on the hot plate test in mice, while it did enhance the effect of morphine. The analgesic effects of morphine and pentazocine on the tail pinch test in rats were potentiated with 0.1 and 1 mg/kg of flunitrazepam. Flunitrazepam had no effect on bradykinin-induced nociceptive response in rats, while 1 mg/kg of the drug enhanced morphine analgesia in this test. Combined effect of flunitrazepam on activities of anesthetics and analgesics may contribute to the clinical effect of this drug in cases of preanesthetic medication.
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  • Susumu OKABE, Haruyo KUNIMI, Hiroshi OHTSUKI
    1981 Volume 77 Issue 4 Pages 397-406
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Ranitidine at 100 to 200 mg/kg (i.d. or p.o.) potently inhibited the development of Shay ulcers, indomethacinor phenylbutazone-induced gastric ulcers and histamine-carbachol-induced duodenal ulcers in rats. Ranitidine at 100 mg/kg (p.o.) also inhibited the development of water-immersion stress-induced gastric ulcers in rats, histamine-induced gastric and duodenal ulcers in guinea pigs, even though the inhibition rate remained within 70%, At that time, the gastric acid output in guinea pigs was reduced with some doses of the drug. Cimetidine at 100 to 200 mg/kg (p.o.) also inhibited the development of indomethacin-, phenylbutazone-, and waterimmersion stress-induced gastric ulcers in rats and histamine-induced gastric and duodenal ulcers in guinea pigs. Shay ulcers and histamine-carbachol-induced duodenal ulcers in rats were not affected by cimetidine. Both ranitidine and cimetidine inhibited the gastric acid output in pylorus-ligated rats (7 hr) ; the maximal inhibition being 79.6% and 50.7% respectively. The mechanism by which ranitidine inhibits various experimental ulcers might be mainly the inhibition of gastric secretion. Gefarnate at 300 mg/kg (p.o.) significantly inhibited phenylbutazone-induced gastric ulcers in rats but had no effect on other ulcer models.
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  • Yoshio SUZUKI, Tadashi NAGAMATSU, Toshihiro KITO, Toshifumi KOHMURA, M ...
    1981 Volume 77 Issue 4 Pages 407-417
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Anti-rat glomerular basement membrane (GBM) rabbit serum was produced by immunizing rabbits with the supernatant substance of trypsin-digested rat GBM. Nephritis was induced in rats by a single intravenous administration of 0.25 ml of anti-serum and changes in pathohistological and biochemical parameters during the process of the disease were investigated in comparison with those of Masugi nephritis and the modified type of Masugi nephritis previously reported. In light microscopic studies, histological changes seen in the kidneys closely resembled those of typical human glomerulonephritis. Changes such as hypercellularity, adhesion between capillary wall and Bowman's capsule, crescent formation and hyalinization in glomeruli and interstitial infiltration were the most pronounced on the 30th day after the anti-serum injection. In immunofluorescent studies, a linear fixation of rabbit IgG was observed along the GBM from the 1st day and the staining of a certain intensity was preserved throughout the experimental periods. A linear staining with anti-rat IgG serum was recognized from the 10th day. The fixation of fibrinogen was also seen in not only the glomerular capillary walls, but also in Bowman's space after the 10th day. Proteinuria significantly increased from the 1st day, reached a peak of 12 times the control level, and thereafter gradually decreased. The patterns of progress of urinary alkaline phosphatase and N-acetyl-β-glucosaminidase activities were much the same as those seen in cases of proteinuria and the levels at their peak times were about 10 and 3 times control levels, respectively. Plasma urea nitrogen level transiently increased on the 5th day and then reverted to the control level by the 30th day. Plasma cholesterol levels were significantly high from the 5th to the 20th days. It is concluded that glomerular damages in this model are more severe, so-called, “nephritic type” and continue for longer periods than in cases of Masugi nephritis, however, do not differ in degree and duration from findings in the modified type of Masugi nephritis.
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  • Mikio ITO, Eiji YOKOCHI, Toshihiro KITO, Yoshio SUZUKI
    1981 Volume 77 Issue 4 Pages 419-425
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    In order to elucidate the role of blood coagulation system in the development and aggravation of glomerulonephritis, liquoid (Liq) was repeatedly administered to normal or nephritic rats. When Liq 10 mg/kg was given i.v. daily × 22 to normal rats (group I), the urinary excretions of protein and N-acetyl-β-glucosaminidase and urea nitrogen content did not significantly change as compared with those in the normal control group. In rats given Liq 10 mg/kg i.v. either every 3 days × 8 (group III) or every day × 22 (group IV) from the 15th day after the i.v. administration of anti-rat glomerular basement membrane rabbit serum (AGS) [0.5 ml/150g body weight], these biochemical parameters were not significantly different from those of nephritic control rats given AGS only (group II). The deposits of fibrin or fibrinoids in glomeruli of groups I, II, III and IV, examined by a fluorescence antibody technique were evident in 2, 2, 8 and 10, respectively, out of 10 rats in each group, although the degree of deposition was slight. Under light microscopy, the adhesion between the glomerular capillary wall and Bowman's capsule, hypercellularity, crescent formation and hyalinization were demonstrated in a part of glomeruli, even in group I. Concerning the influence of Liq in nephritic rats, the most prominant glomerular change was hyalinization. While in group II the hyalinization was evident in only 17% of glomeruli, in groups III and IV the hyalinization was 41 and 55%, respectively. Although no significant difference was seen between groups II and III regarding other glomerular changes except for hypercellularity, these changes in group IV increased as compared with those in group II. However, hypercellularity was less in groups III and IV than in group II. A slight occlusion of the glomerular capillary lumen was observed, even in group I. In nephritic groups, the degree of the capillary lumen occlusion in group I V was greater than that in group II. From these results, the acceleration of intraglomerular blood coagulation is considered to be a major factor in the development and aggravation of glomerulonephritis.
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  • Kumeji TAKEUCHI, Hiroshi KOGO, Yoshio AIZAWA
    1981 Volume 77 Issue 4 Pages 427-434
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    The effect of methylxanthines (theophylline, theobromine, caffeine) on urinary prostaglandin E (PGE) excretion in rats was investigated. Male rats, weighing 270-300g only were used. Food was withdrawn 3 hr before the experiment and water intake was free during the test period. In saline or water loaded experiments, 0.9%, 9% NaCl solution or water containing each drug was administered orally in a volume of 2.5ml/100g. The urinary PGE was measured by bioassay using rat stomach fundus strip. In rats loaded with isotonic saline, the urinary PGE excretion was increased by methylxanthines and the greatest effect was seen with theophylline. The effect of theophylline on PGE excretion was evident in non-loaded and isotonic saline-loaded rats. In particular, the percentages of PGE, sodium and chloride in the urine were remarkably increased, as compared with findings in the control. In non-loaded and isotonic saline-loaded rats, the urinary PGE excretion induced by theophylline correlated significantly with the sodium and chloride excretion. These results suggest the participation of renal PGE in the effects of theophylline on kidney function.
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  • Yoshito NAKAGAWA, Keisuke TAKEDA, Hiroshi SAKURAI, Akio MITOMI, Shoich ...
    1981 Volume 77 Issue 4 Pages 435-445
    Published: 1981
    Released on J-STAGE: March 09, 2007
    JOURNAL FREE ACCESS
    Effects on blood pressure and heart rate of labetalol, a new beta-adrenoceptor blocking agent with α-blocking action were studied in conscious hypertensive rats (SHR, DOCA-hypertensive rats and renal hypertensive rats (RHR)). Labetalol with two asymmetric carbon atoms consists of an equal proportion of two racemates. In SHR, prevention of the development of hypertension was noted after 1.5 weeks of chronic oral administration of labetalol 25, 50 and 100 mg/kg/day, while bradycardia occurred beginning with the day of administration. Thus, the prevention of the development of hypertension appeared much earlier than in the case of the other β-blockers. Antihypertensive effects and bradycardia were also noted in DOCA hypertensive rats and RHR after oral administration of Labetalol 10, 30 and 100 mg/kg/day for six days. In DOCA hypertensive rats, the antihypertensive effect was more pronounced than in the RHR. These findings are in contrast to those obtained with other β-blockers. Other β-blockers produced antihypertensive effects only in SHR. It is concluded that not only the β-blocking action, but also the α-blocking action of labetalol plays an important role in the antihypertensive effects of labetalol.
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