Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 90, Issue 2
Displaying 1-7 of 7 articles from this issue
  • Hiroshi KUROMI
    1987 Volume 90 Issue 2 Pages 73-81
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    This paper summarizes the hypothesis proposed to explain the mechanism for AChR localization at the neuromuscular synapse. Two theories have been proposed to explain the neuronal control of extrajunctional AChR. One theory claimed that motoneurons decreased the ACh sensitivity of the extrajunctional membrane through neurotrophic influence. However, direct electrical stimulation of denervated muscles resulted in a decrease of extrajunctional ACh sensitivity, supporting the other hypothesis that loss of extrajunctional AChR of the innervated muscle is directly related to muscle activity per se. AChR clusters (high density of AChR) at the neuro-muscular junction were supposed to result from the association of nerves with preexisting AChR clusters. However, Xenopus nerve-muscle cocultures clearly demonstrated that AChR clusters at the neuromuscular junction were formed after the nerve came in contact with the muscle membrane. Two hypothesis are proposed for nerve-induced formation of AChR clusters. Preferential insertion of AChR into the end-plate was suggested by the finding that AChR messenger RNA was more abundant near to than far from the end-plate in adult muscle fibers. On the other hand, in cultured and embryonic muscles, AChR clusters were formed at nerve-muscle junctions through receptor redistribution which was mediated by the passive diffusion-trap mechanism.
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  • Emiko FUJII, Fujiko TSUKAHARA, Teruko NOMOTO
    1987 Volume 90 Issue 2 Pages 83-89
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The present study deals with the hypnotic effect of pentobarbital (Pento) in relation to its metabolism in hepatic microsomes in streptozotocin (STZ, 170 mg/kg, i.p.) injected mice. Liver weight (mg/10 g body wt.) of STZ-treated mice was larger than that of the controls throughout the experimental period. Although the shortening of sleeping time induced by Pento (60 mg/kg, i.p.) was always observed, Pento-metabolizing enzyme activity (by the method of Kato et al., 1964) increased in mice with diabetes for 2 and 4 weeks but decreased in mice with diabetes for 8 weeks. Induction following phenobarbital (100 mg/kg, s.c.) and inhibition by SKF 525-A (10 mg/kg, i.p.) of hepatic metabolizing enzyme were found in both control and mice with diabetes for 2, 4 and 8 weeks, but these were not definitely correlated to their hepatic Pento-metabolizing enzyme activities. STZ-induced hyperglycemia and shortening of sleeping time by Pento were completely prevented by the pretreatment with nicotinamide (500 mg/kg, i.p.). NPH-insulin injection partially decreased hyperglycemia in STZ-diabetic mice, but sleeping time by Pento was not significantly affected. These results suggest that the hyposensitivity to Pento in STZ-diabetic mice is partially related to an abnormality of metabolism in liver such as the hyperglycemic state.
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  • Hiromi SATO, Masao NAKANO, Ikuko HORITA, Jiro TAKAHASHI, Koei MORIGUCH ...
    1987 Volume 90 Issue 2 Pages 91-95
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The present investigation was undertaken to examine the recovery of functions, spontaneous EEG activity and cerebral ATP content during blood recirculation following cerebral ischemia in rats. The ischemia was induced by bilateral carotid artery 30 min-occlusion 24 hr after the permanent electrocauterization of bilateral vertebral arteries. EEG spectral analysis was performed by the Berg transform. The recovery of EEG activity was assessed by the time elapsing from the onset of blood recirculation until the δ (0.5 ?? 4 Hz), θ (4 ?? 8 Hz), α (8 ?? 13 Hz) or β (13 ?? 32 Hz) band reappeared and the relative proportion of the four bands at 45 and 60 min after recirculation. Following the 20 min recirculation, the brains were frozen in situ with liquid nitrogen and then stored at -80°C for later extraction for analysis. Concentrations of ATP in the cerebral cortex were determined with enzymatic methods. In animals administered FO-1561 (10 ?? 100 mg/kg, i.v.) simultaneously with blood recirculation, the reduction of time elapsing until reappearance of the θ, α and β bands, the decrease in proportion of the δ band and the increase in that of the θ, α and β bands which indicated the facilitation of transition to the normal state were observed. In animals administered FO-1561 (100 mg/kg), the improvement of ATP content was detected. These results demonstrate that FO-1561 may have a beneficial effect on the recovery from dysfunctions due to cerebrovascular disorder.
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  • Katsuhiko TANIGUCHI, Misuzu URAKAMI, Koichiro TAKANAKA
    1987 Volume 90 Issue 2 Pages 97-103
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    The aim of this study was to examine the effects of antiallergic agents on the functions of polymorphonuclear leukocytes (PMNs) in terms of its arachidonic acid release and superoxide-anion generation. The stimulations of arachidonic acid release by formylmethionyl-leucyl-phenylalanine (FMLP) were effectively diminished by 20 μM of azelastine as well as clemastine. Challenges of 20 μM and 50 μM of these agents inhibited approximately 50% and 100% of the arachidonic acid release, respectively. On the contrary, inhibitions of over 50% were not caused by cromoglycate, chlorpheniramine and diphenhydramine at concentrations up to 50 μM. The potency of the above examined drugs on the superoxide generations from PMNs were similar to the effects on arachidonic acid release. Ketotifen, however, showed intermediate effects indicating that a challenge of 50μM ketotifen inhibited approximately 50% of the arachidonic acid release without having an effect on the superoxide generation. These experimental observations suggested that one of the important roles of the antiallergic agents including azelastine (known as a chemical mediator release inhibitor) and clemastine (known as a histamine H1 receptor antagonist) could be an inhibition of the first step of the arachidonic acid cascade.
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  • Tsuyoshi NAGASE, Jiro ISHIKO, Shuji TAKAORI
    1987 Volume 90 Issue 2 Pages 105-114
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    Studies were performed to elucidate the effects of 1-[2-[bis (fluorophenyl) methoxy] ethyl]-4-(3-phenylpropyl) piperazine dihydrochloride (I-893), a newly synthesized aryl-1, 4-dialkylpiperazine derivative, on turnover of dopamine and norepinephrine in the rat brain. The contents of both monoamines were not affected by I-893 at an oral dose of 10 mg/kg. The oral administration of 50 ?? 250 mg/kg produced a transient increase in dopamine content of the caudate nucleus and hypothalamus, and thereafter, the content dosedependently decreased. Norepinephrine levels in the hypothalamus and frontal cortex were slightly decreased by I-893. I-893 potentiated the rate of α-methyl-p-tyrosine-induced depletion of dopamine and norepinephrine. The 3-methoxytyramine content in animals treated with pargyline was increased by 1-893 in the caudate nucleus and olfactory tubercle. NSD-1015-induced accumulation of DOPA was suppressed by larger doses of I-893. Oral administration of I-893 (10 ?? 250 mg/kg/day) for 14 days slightly attenuated the inhibitory effects of the drug on the norepinephrine level, while it did not affect the inhibitory effect on the dopamine level. These results suggest that I-893 facilitates the release of dopamine and norepinephrine and/or inhibits the uptake of the monoamines in the presynaptic nerve terminals.
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  • Effect of reduced proscillaridins on guinea-pig hearts
    Jinsaku SAKAKIBARA, Jun MORI, Shin-ichi NAGAI, Yoshihiro HOTTA, Kazumi ...
    1987 Volume 90 Issue 2 Pages 115-123
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    Five hydrogenated proscillaridins (bufa-4, 20-dienolide (PH21), bufa-4, 20 (22)-dienolide (PH22), 20R-bufa-4-enolide (PH4-R), 20S-bufa-4-enolide (PH4-S), chola-4-enoate (PH4-E)) were prepared semi-synthetically, and their pharmacological effect was studied using guinea pigs. The positive inotropic effect (PIE) was examined in papillary muscles isolated from guinea-pig hearts. These compounds produced PIE, dose-dependently; the Dose-PIE curve was characterized by a faster PIE development than that by the parent compound proscillaridin (PS). The concentrations at which half maximum PIE just developed (pD2) were as follows : PS, 7.4; PH22, 6.2; PH21, 5.8; PH4-R, 5.3; PH4-E, 5.0; and PH4-S, 4.9. The time required to the half maximum effect (T50) at a given concentration of pD2 was measured in min: PS, 33; PH4-E, 22; PH22, 15; PH21, 7; PH4-S, 7; and PH4-R, 2. The speeds of inotropy of these compounds depended on the position of lactone ring reduction, though they have the same lipophilicity (Rm). Concentration-PIE curves of reduced PS-compounds were characterized by a decrease in potency and an increase in efficacy. PH21 and PH4-R produced PIE over wider range of concentrations than those of the other compounds. When PH21 at the dose of 11.9 mg/kg, an equivalent dose of 4.4 times the pD2 values, was administrated intravenously by bolus injection into guinea pigs, no arrhythmias were observed on the ECG. The administration of PH22 at the dose of 5.1 mg/kg (at 4.4 times dose of pD2), however, resulted (in an earlier stage after injection) in ventricular rhythms. These results suggest that PH21 has dose-dependent PIE over a wide range of concentrations.
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  • Yukitaka HIYAMA, Hiroshi WATANABE, Keiko MIURA, Shouei SUGITA, Kou-ich ...
    1987 Volume 90 Issue 2 Pages 125-132
    Published: 1987
    Released on J-STAGE: February 23, 2007
    JOURNAL FREE ACCESS
    Behavior improvement from apomorphine-induced rotation, morphological features of nerve cells and in vivo release of dopamine (DA) were examined after the implantation of neuronal cell suspensions into the striatum of female rats with 6-hydroxydopamine lesions. Apomorphine-induced rotation was significantly suppressed in 11 out of 26 rats from two through ten weeks after the implantation. In 3 out of 26 rats, the rotation was significantly suppressed for four weeks after the implantation, although the suppression was reversed by the fifth week. In the remaining 12 rats, the rotation was not inhibited after the implantation. Behavior improvement was concurrent with extension of neurites from anti-DA immunopositive cells to the host caudate. Anti-DA cells were very scant in the absence of behavior improvement. In vivo release of DA and the metabolites, 3, 4-dihydroxyphenylacetic acid and homovanillic acid, was detected in the perfusates of the striatum of the animals that were functionally improved by the transplant. Methamphetamine caused an increase in DA release and a decrease in the release of the metabolites in those animals. These results suggest that grafted neuronal cells which are sensitive to methamphetamine probably innervate neuronal elements in the host caudate, and the release of DA from these grafted cells functionally affects behavior improvement.
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