Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 102, Issue 6
Displaying 1-7 of 7 articles from this issue
  • Kohji FUKUNAGA
    1993 Volume 102 Issue 6 Pages 355-369
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Both Ca2+/calmodulin-dependent protein kinase II (CaM kinase II) and protein kinase C (PKC) have been implicated as possible candidates for contributing to the induction of long-term potentiation (LTP) in the hippocampus. The induction of LTP in the CA1 region of the hippocampus, an event which requires postsynaptic Ca2+ influx through NMDA-type glutamate receptors, is blocked by calmodulin antagonists and inhibitors of CaM kinase II and PKC. In the present study, we describe the activation characteristics of CaM kinase II and PKC through the stimulation of glutamate receptors and regulation of the phosphorylation of substrates for CaM kinase II in the hippocampus. In cultured rat hippocampal neurons, glutamate elevated the Ca2+-independent activity of CaM kinase II through autophosphorylation, and this response was blocked by specific antagonists of the NMDA receptor. In addition, glutamate stimulated the translocation of PKC from the cytosol to the membrane fraction through the metabotropic glutamate receptor. In the experiments with 32P-labeled cells, the phosphorylation of microtubule-associated protein 2 (MAP2) and synapsin I was stimulated by the exposure to glutamate. Finally, we demonstrated that high, but not low, frequency stimulation applied to two groups of CA1 afferents in the slices resulted in the induction of LTP with concomitant long-lasting increases in the Ca2+-independent and total CaM kinase II activities as well as the autophosphorylation. It could be blocked by preincubation of the slices with NMDA-receptor antagonist. These results suggest that glutamate can activate CaM kinase II through NMDA receptors in the induction of LTP and in turn stimulates the phosphorylation of target proteins such as MAP2 and synapsin I.
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  • Shigetoshi CHIBA
    1993 Volume 102 Issue 6 Pages 371-378
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    A new perfusion technique for isolated vascular preparations is described. The cannula inserting method developed by Hongo and Chiba (J. Pharmacol. Methods 9, 83, 1983) and modified by Tsuji and Chiba (Japan. J. Pharmacol. 34, 95, 1984) is useful for observing vascular reactivity in perfused, isolated vessels. In this method, 1) applied substances act only from the intraluminal side; 2) vascular responses to substances, not only constriction but also dilatation in non-treated preparations, are readily obtainable by a single injection of active substances; and 3) the vascular reactivity is reproducible over 7-8 hr at 37 °C. Our modified cannula inserting methods are slso described.
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  • Kenichi INUI, Akihiko MATSUDA, Hirotaka CHAKI, Ichirou MAKITA, Yukifum ...
    1993 Volume 102 Issue 6 Pages 379-388
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Using portacaval anastomosis (PCA) rats as a model with or without injection of ammonium acetate, we investigated the effects of MHS-G on the abnormalities of electroencephalogram (EEG) and brain amines metabolism in comparison with those of SF-1008C, a commercial nutritional preparation for hepatic failure. MHS-G (0.68 g/kg, p.o.) clearly improved both the abnormalities of EEG (such as reduction of amplitude, increasing δ wave distribution and decreasing β wave distribution) and brain amines metabolism (such as increasing of Trp and DOPAC content) after injection of ammonium acetate. Moreover, MHS-G significantly increased branched chain amino acid concentrations and decreased aromatic amino acid concentrations in plasma and brain in comparison with water, and it significantly decreased the ammonia level in plasma in comparison with water and SF-1008C. These results suggest that MHS-G has a positive effect on abnormalities of EEG and amino acids metabolism in the plasma and brain of PCA rats.
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  • Hideaki FUJISAKI, Kiyoshi OKETANI, Hisashi SHIBATA, Manabu MURAKAMI, M ...
    1993 Volume 102 Issue 6 Pages 389-397
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The inhibitory action of (±)-sodium 2-[{4-(3-methoxypropoxy)-3-methylpyridin-2-yl} methylsulfinyl]-1H-benzimidazole (E3810) on H+, K+-ATPase and gastric acid secretion in vitro was investigated, and it was compared with those of omeprazole (OPZ). E3810 concentration-dependently inhibited the H+, K+-ATPase activity of hog gastric vesicles. Its IC50 was 0.26 μM at pH 6.1. The inhibition was irreversible in nature and reversed by dithiothreitol. The potency of E3810 was 10-times that of omeprazole. Acidification of the intravesicular (luminal) space increased 1000-fold the potency of E3810, indicating that E3810 is a specific inhibitor which binds to the luminal cysteine residue of H+, K+-ATPase. Prolonged incubation of up to 180 min in the absence of thiol reagents of rabbit gastric glands which had been inhibited by a low concentration of E3810 (0.3 and 0.5 μM) time-dependently and completely reversed the inhibition, as determined by aminopyrine uptake, whereas it did not recover the acid secretion in omeprazole-treated glands. These results suggest that the acid-activated E3810 is a potent specific inhibitor of H+, K+-ATPase, and that the duration of the inhibitory action of E3810 is much shorter than that of omeprazole in isolated gastric glands.
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  • Yasuyuki SUZUKI, Yuki HAYAKAWA, Tsutomu OYAMA, Tomoko ISONO, Yuji OHMI ...
    1993 Volume 102 Issue 6 Pages 399-404
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    Tsumura Shuchi-Bushi Powder for Ethical Dispensing” (TJ-3021) is an herbal drug of processed Aconiti tuber that attenuates its toxicity. A greater part of mesaconitine which is regarded as a main analgesic component in processed Aconiti tuber is hydrolyzed into benzoylmesaconine (BM) by its processing. In this study, the analgesic effect of BM was examined in comparison with that of TJ-3021 in mice and rats. BM (10 mg/kg, p.o.) depressed the acetic acid-induced writhing significantly. Its analgesic activity was almost similar in magnitude to that of TJ-3021 (300 mg/kg, p.o.). BM (30 mg/kg, p.o.) significantly increased the pain threshold ratio of paw pressure in repeated cold stress (RCS) rats, and its analgesic potency appeared to be equivalent to that of TJ-3021 (1000 mg/kg, p.o.). These results suggest that the analgesic activity of BM is strong enough for explanation of the analgesic effect of TJ-3021, and it might contribute to that of TJ-3021.
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  • Minoru WATANABE
    1993 Volume 102 Issue 6 Pages 405-411
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The present study was performed to investigate the effects of submaxillariectomy (Subx) on the anesthetic effect (sleeping time) of pentobarbital, the concentration-time profile of plasma pentobarbital and the hepatic drug metabolizing enzyme systems in male rats of the Donryu strain. Subx was performed when the rats were 60 days old. Subx prolonged the duration of pentobarbital (30 mg/kg, i.p.) anesthesia at 10, 23 and 43 days after the operation, respectively. At 43 days after Subx, the plasma pentobarbital concentration was higher in the Subx group until 30 min after the administration. There was no significant difference in the hepatic microsomal cytochrome P-450 content between the Subx and control groups. Cytochrome b5 content, aminopyrine N-demethylase and aniline hydroxylase activities were increased significantly in the Subx group. The activity of heme oxygenase, the rate limiting enzyme in the heme catabolic pathway, tended to increase in the Subx group. Furthermore, the activity of δ-aminolevulinic acid synthetase, the rate limiting enzyme in the heme synthetic pathway, was significantly decreased to 51 percent of the control group by Subx. These results may suggest that the prolongation of the duration of pentobarbital anesthesia is caused by Subx due to the change in the pharmacokinetics of pentobarbital, especially the inhibitory effects of the hepatic pentobarbital metabolizing enzyme system.
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  • Go KITO, Masao TANABE, Zen-ichi TERASHITA
    1993 Volume 102 Issue 6 Pages 413-420
    Published: 1993
    Released on J-STAGE: February 06, 2007
    JOURNAL FREE ACCESS
    The effects of CV-4151 on post-ischemic brain hypoperfusion and thromboxane (Tx)A2 production in a canine model of total global brain ischemia were studied. Complete cerebral ischemia for 5 min was produced in adult mongrel dogs by temporary ligation of the venae cavae and aorta. In the non-treated group, cerebral blood flow (CBF) increased during the first 20 to 30 min post-ischemia followed by a gradual decline and then stayed below preischemic level; CBF at 2 hr after the reperfusion was significantly reduced to ca 77% of the pre-ischemic level. Water content in the cerebral cortex at 2 hr after the reperfusion in the non-treated group was 78.15±0.21%, higher than the content in the control group, 76.70±0.07 %. The concentration of TxB2 in the sagittal sinus was significantly increased at 30 min post ischemia. CV-4151 (1.0 mg/kg, i.v.) almost completely inhibited the post-ischemic hypoperfusion, significantly inhibited the increase in water content and almost completely inhibited the production of TxB2 in the post-ischemic period and increased the production of 6-keto PGF. OKY-046 (10 mg/kg, i.v.) had no significant effects on both post-ischemic hypoperfusion and increase in water content in the cerebral cortex. We conclude that CV-4151 ameliorates post-ischemic cerebral hypoperfusion and that this improvement is associated with decreased sagittal sinus levels of TxB2.
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