Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 85, Issue 3
Displaying 1-9 of 9 articles from this issue
  • Yomei TAKE, Masaki SHIBOTA, Akinobu NAGAOKA, Yuji NAGAWA
    1985 Volume 85 Issue 3 Pages 111-117
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Regional cerebral blood flow (rCBF) was measured prior to, during and after global cerebral ischemia in rats. Global cerebral ischemia was produced by 10 or 30-min occlusion of both common carotid arteries which was done 24 hr after the permanent electrocauterization of bilateral vertebral arteries. The rCBF was measured using the radioactive microsphere technique. In rats subjected to 10-min cerebral ischemia, rCBF in 9 brain regions was reduced to 11.3-54.8% (mean: 26.9%) of that of the sham operated control. Ten min after recirculation, hyperperfusion was observed in the cerebral cortex, hippocampus and striatum, and a moderate recovery was detected in the n.accumb.+olfactory tub., thalamus and hypothalamus. However, rCBF in these 6 regions was again decreased 20-30 min later, and it recovered to levels more than 50% of the control 60 min after the ischemic event. In the other 3 regions (cerebellum, colliculus sup.+inf., pons+medulla), rCBF increased toward the control level gradually, and it completely recovered 60 min after recirculation. On the other hand, in rats subjected to 30 min cerebral ischemia, rCBF in 9 brain regions was reduced to 1.77-26.3% (mean: 9.6%) of that of the control. The post-ischemic hyperperfusion in the cerebral cortex and hippocampus and a moderate recovery of rCBF in the striatum and n.accumb.+olfactory tub. were observed 10 min after the cerebral ischemia. However, rCBF in these 4 regions remained under the control levels from 20 to 60 min after recirculation. The change of rCBF in the other regions was similar to that in the 10-min ischemic group, but the recovery was less at 60 min after recirculation. These results indicate that the abnormalities in the post-ischemic rCBF may be involved in the behavioral, EEG and neurochemical changes observed after the cerebral ischemia.
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  • Kazumi IWAKI, Yukio YONETANI
    1985 Volume 85 Issue 3 Pages 119-127
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The effect of consecutive treatments with thiazide diuretics on renal handling of uric acid was investigated with clearance experiments using rats. Two weeks of oral administration of trichlormethiazide (2 mg/kg, twice a day) in rats fed an ordinary diet caused no change in the uric acid excretory capacity. However, a week of oral administration of trichlormethiazide (0.1, 0.5 and 2 mg/kg, twice a day) in rats maintained on a purified diet containing low sodium amounts decreased the fractional excretion of uric acid. At 2 mg/kg, the decrease of inulin clearance developed clearly. Similar treatments with hydrochlorothiazide (10 mg/kg) and cyclopenthiazide (0.5 mg/kg) also decreased the inulin clearance and the fractional excretion of uric acid. Administration of the above diuretics during sodium deprivation resulted in a marked rise of the hematocrit and hypokalemia. Purified diet containing low sodium amounts alone did not change the uric acid excretory capacity as compared to the ordinary diet. Trichlormethiazide treatment and continued sodium deprivation caused marked losses of body weight and food intake and promotions of urine output and water intake. Histologically, hyperplasia of the cells and tubular dilatation at macula densa were slightly developed during sodium deprivation. With these severe changes, dilatation of the proximal tubules with flattened and regenerated epithelium was shown by the trichlormethiazide treatment (0.5 mg/kg). From these results, the characteristics of chronic treatment with thiazide diuretics acting on renal uricacid retention could be understood in the rat under sodium deprivation.
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  • Effects on central dopaminergic system-dependent behaviors in rats and mice
    Masaomi MIYAMOTO, Yoshiaki SAJI, Yuji NAGAWA
    1985 Volume 85 Issue 3 Pages 129-141
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of TRH and its analog, γ-butyrolactone-γ-carbonyl-histidyl-prolinamide citrate (DN-1417), on circling, stereotyped or climbing behavior were investigated in rats and mice. High doses of TRH (100 mg/kg, i.p.) and DN-1417 (20 ?? 50mg/kg, i.p.) produced a significant ipsilateral circling behavior in rats with the lesions of the unilateral dopamine (DA) pathway by 6-hydroxydopamine. In intact mice, stereotyped sniffing accompanying hyperactivity was caused at low doses of TRH or DN-1417 (1 ?? 20 mg/kg, i.p.), and stereotyped licking behavior was observed at high doses of TRH or DN-1417 (20 ?? 200 mg/kg, i.p.). Furthermore, TRH, DN-1417 or methamphetamine caused a dose-related climbing behavior in mice pretreated with L-DOPA and Ro 4-4602. Circling behavior, stereotyped sniffing or licking behavior induced by TRH or DN-1417 was markedly suppressed by pretreatment with pimozide or α-methyltyrosine. However, atropine and scopolamine potentiated the circling inducing action of TRH or DN-1417, in contrast with suppression of the licking behavior. These results suggest that TRH and DN-1417 produce circling, sniffing, licking and climbing behaviors via activation of the central DA system, and that cholinergic mechanisms may be also involved in licking behavior induced by TRH or DN-1417.
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  • Yomei TAKE, Shigehiko NARUMI, Etsuo KURIHARA, Masaki SHIBOTA, Yoshiaki ...
    1985 Volume 85 Issue 3 Pages 143-157
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    We investigated the ameliorating effects of DN-1417 (a TRH analog) on the changes of behavior, EEG, neurochemical parameters and regional cerebral blood flow (rCBF) in rats with global cerebral ischemia. Global cerebral ischemia was produced by 10-min occlusion of both common carotid arteries 24 hr after the permanent electrocauterization of bilateral vertebral arteries. DN-1417 was administered intraperitoneally as soon as possible, following recirculation of carotid blood flow. DN-1417 shortened significantly the recovery times of righting reflex (RR) and spontaneous movement (SM) at 2.5 mg/kg and higher doses, and it recovered effectively the EEG activity at 10 mg/kg during recirculation after 10-min cerebral ischemia. In addition, DN-1417 (10 mg/kg) recovered the various changes such as decrease of 5-hydroxytryptamine (5-HT) levels, increase of cyclic AMP (cAMP) levels, inhibition of [3H]-choline uptake, depression of choline acetyltransferase (CAT) and acetylcholine esterase (AChE) activities, and shortened the durations of hyperperfusion and hypoperfusion of rCBF. As a result, it is identified that DN-1417 ameliorates the disturbance of consciousness supposedly caused by behavioral and EEG abnormalities during recirculation following the temporary cerebral ischemia, and the effect of DN-1417 seems to be mediated by normalizing of alterations in the brain monoaminergic and cholinergic systems, as well as rCBF, and the effectiveness for disturbance of consciousness in clinical situations would be expected.
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  • Yohji MIURA, Jun INUI, Tadao NAKAMURA
    1985 Volume 85 Issue 3 Pages 159-165
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of nizofenone, an agent which has been known to have a protective effect against experimental cerebral isehemia or anoxia, on the action potential of guinea-pig papillary muscle and S-A node and dog Purkinje fibers were studied. Nizofenone (10-6 and 10-5M) significantly prolonged the action potential duration of guinea-pig papillary muscle and dog Purkinje fibers accompanying prolongation of the effective refractory period in dog Purkinje fibers. Nizofenone decreased Vmax at the concentrations of 10-5 and 10-4M in guinea-pig papillary muscle and at 10-4M in dog Purkinje fibers. Nizofenone suppressed the spontaneous activity of dog Purkinje fibers and guinea-pig S-A node at the concentrations of 3×10-5 to 10-4M and 10-5M, respectively. Nizofenone (10-4M) decreased the contractile force of guinea-pig papillary muscle. In the guinea-pig papillary muscle, the effect of nizofenone on action potential duration was almost the same as that of quinidine, but the inhibitory effect on Vmax was slightly weaker than quinidine. These results suggest that nizofenone has a so-called “quinidine-like action” on cardiac membrane.
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  • Ikuo TANAKA, Hiroyuki TAGAMI
    1985 Volume 85 Issue 3 Pages 167-171
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Effects of TKG01 on gastric ulcers and gastric secretion in rats were investiagted in comparison with those of TA903, which is the equimolar clathrate compound of TKG01 anhydride with β-cyclodextrin. The doses were adjusted on a molecular weight basis to include the same amount of TKGOI anhydride. Water-immersion stress ulcers were dose-dependently (100, 300 mg/kg) inhibited by TA903 given orally, but only significantly inhibited by TKG01 (300 mg/kg). TA903, given orally, even in low doses (30, 100 mg/kg) potently inhibited HCl-ethanol ulcers, whereas TKG01 did not inhibit these ulcers. Both TA903 and TKG01, given orally (100, 300 mg/kg), showed similar inhibition of indomethacin ulcers. TA903, given intraduodenally (100, 300 mg/kg), dose-dependently inhibited gastric secretion (volume, acid output and pepsin output) in pylorus-ligated rats, but TKG01 only inhibited pepsin output (100, 300 mg/kg). These results showed that TA903 had a broader spectrum of anti-ulcer effects than TKG01 and the mechanism of TA903 could involve both its cytoprotective activity and its antisecretory effect.
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  • Yasuko KOHNO, Yasuyuki NOMURA, Tomio SEGAWA
    1985 Volume 85 Issue 3 Pages 173-183
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    After cerebral cortical membranes were incubated with 0.1-100 μM of dopamine (DA) in 50 mM Tris-HCl buffer (pH 7.7) at 37°C for 30 min, [3H] clonidine binding to α2-receptors was increased in a concentration-dependent manner without changing [3H] WB4101 and [3H] DHA binding to α1- and β-receptors, respectively. Scatchard analysis of [3H] clonidine binding to cortical membranes showed that DA increased the Bmax in both high- and low-affinity components. The increasing effect of DA on [3H] clonidine binding was dependent on incubation time and temperature, and it was antagonized by pimozide and cis-flupenthixol. The addition of GTP produced a reduction in DA-induced elevation in [3H] clonidine binding, while that of cyclic AMP did not affect the effect of DA. DA and Mn2+, though both of them increased [3H] clonidine binding, appeared to act at a different site in the membrane. Furthermore, the DA-induced increase in [3H] clonidine binding was found uniformly in membranes prepared from 7 other regions of the rat brain. These results suggested that DA regulates specifically α2-receptor density by stimulating D1-receptors and/or via other mechanism(s).
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  • Kohei UMEZU, Satoshi YUASA, Atsuko SUDOH
    1985 Volume 85 Issue 3 Pages 185-192
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    Tritoqualine (TRQ) adiministered at doses of 100 or 200 mg/kg, perorally, had a preventive effect on the liver injury in rats induced by the treatment with CCl4 for 12 weeks consecutively. Rats subjected to this chronic treatment with CCl4 showed a decrease in body weight gain and changes in several serum parameters that are indicators of hepatic function were observed: the increase of transaminases, as a parameter of hepatocyte breakdown; the increase of alkaline phosphatase, as a parameter of biliary system abnormalities, the reduction of prothrombin time, as a marker of protein biosynthesis in the liver; and the change of lipids concentrations, reflecting liver injury. After the administration of TRQ perorally, there was a notable suppression of the increment in leaked enzymes in the serum and a marked improvement of the parameters concerning protein biosynthesis and lipid metabolism in comparison with CCl4 control rats. Marked fibrosis in the liver was observed after CCl4 treatment for 12 weeks, and the collagen content in the liver was 5 times higher than that of control rats. TRQ suppressed the increment in collagen formation and also showed improvement of the decrease of the liver function with regards to protein biosynthesis in CCl4-treated rats. Judging from these results, it was concluded that TRQ had a remarkable protecting action on the liver injury chronically induced by CCl4 treatment and was a effective compound for restoring liver function.
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  • Effects of wuweizisu C, a lignan component of schizandra fruits, on experimental liver injuries in rats
    Shigefumi TAKEDA, Shyuji FUNO, Akira IIZUKA, Yoshio KASE, Ichiro ARAI, ...
    1985 Volume 85 Issue 3 Pages 193-208
    Published: 1985
    Released on J-STAGE: March 02, 2007
    JOURNAL FREE ACCESS
    The effects of wuweizisu C, a lignan component of schizandra fruits, on liver injuries induced by carbon tetrachloride (CCl4), d-galactosamine and dl-ethionine were investigated by means of serum-biochemical and histopathological examinations in rats. Pretreatment or combined administration of wuweizisu C dose-dependently reduced the elevation of serum transaminase activity and histological changes such as fatty degeneration, cell necrosis, inflammatory cell infiltration, etc., which were caused by the single administration of 1 ml/kg, p.o., or the repeated administration of 0.2 ml/kg, s.c., daily for 4 days of CCl4, respectively. The effects of wuweizisu C on the liver injuries induced by a low dose (200 mg/kg, i.p.) and a high dose (400 mg/kg, i.p.) of d-galactosamine were compared with those of uridine. Wuweizisu C significantly lowered the rise of serum transaminase activity after the administration of a low dose of d-galactosamine in the serum-biochemical analysis. A tendency was also shown to inhibit cell necrosis and inflammatory cell infiltration caused by both doses of d-galactosamine in the histopathological examination. On the other hand, uridine markedly repaired the serum-biochemical and histopathological changes after the administrations of both doses of d-galactosamine. Also wuweizisu C cured the liver injury by the repeated administration of 150 mg/kg, i.p., daily for 4 days of d-galactosamine. After the repeated administration of 250 mg/kg, s.c., daily for 4 days of ethionine, liver cell atrophy, diffuse fatty degeneration and decrease of serum triglyceride were observed, but not cell necrosis. Wuweizisu C dose-dependently inhibited fatty degeneration and decrease of serum triglyceride. These findings suggest that wuweizisu C can be protective and/or therapeutic on hepatocellular phenomena such as cell necrosis, fatty degeneration, inflammatory cell infiltration, etc., in human hepatitis.
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