Folia Pharmacologica Japonica
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
Volume 110, Issue 2
Displaying 1-4 of 4 articles from this issue
  • Yukio YONEDA, Kiyokazu OGITA
    1997 Volume 110 Issue 2 Pages 45-57
    Published: 1997
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    In eukaryotes, protein de novo synthesis is mainly controlled at the level of gene transcription by transcription factors in cell nuclei. Transcription factors are nuclear proteins with abilities to recognize particular nucleotide sequences at promoter or enhancer regions on double stranded DNAs, followed by modulation of transcription of their inducible target genes. These transcription factors are categorized into 3 different major classes according to their unique protein motifs. In this article, we have outlined the signal responsiveness of particular transcription factors in the brain. Indeed, nuclear transcription factors rapidly respond to a variety of extracellular signals carried by neurotransmitters, hormones and autacoids as a third messenger in frequent situations. Moreover, delayed neuronal death could involve mechanisms associated with modulation of de novo synthesis of target proteins by the transcription factor activator protein-1 in particular hippocampal subregions after ischemia. Accordingly, it thus appears that transcription factors may play a critical role in long-lasting consolidation of transient signals through modulation of de novo synthesis of inducible target proteins in the brain.
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  • Sachiko OH-ISHI
    1997 Volume 110 Issue 2 Pages 59-68
    Published: 1997
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    Mediators involved in acute inflammation were explored by using rat pleurisies induced by carrageenin or zymosan. The kallikrein-kinin system and eicosanoids were the main mediators responsible for plasma exudation in carrageenin-induced rat pleurisy, while histamine, PAF and the complement system could be the main mediators involved in the vascular permeability increase to cause plasma exudation into the pleural cavity in zymosan-induced rat pleurisy. Several chemokines were detected in the pleural exudates of carrageenin-pleurisy as well as those of zymosan-pleurisy; and exogenous recombinant TNFα, IL-1, IL-6 and CINC induced neutrophil migration into rat pleural cavity. These results suggest that these chemokines, directly or indirectly, may partly cause neutrophil migration in the pleural exudates during carrageenin and zymosaninduced pleurisy. In addition, chemokine production in response to prostanoids and PAF production in response to arachidonic acid were also suggested.
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  • Yasuo WATANABE
    1997 Volume 110 Issue 2 Pages 69-75
    Published: 1997
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    The calmodulin (CaM)-binding domain of rat neuronal nitric oxide synthase (nNOS) was analyzed using 3 synthetic peptides corresponding to different regions of the middle portion of the enzyme. One corresponding to nNOS 732-754 completely inhibited the NOS enzyme activity with an IC50 of about 1μM. Kinetic analysis indicated that the inhibition was not competitive with respect to L-arginine, and the peptide produced a Ca2+-dependent, electrophoretic mobility shift of CaM on 1M urea gels. A specific hydrophobic/basic amino acid cluster in the rat nNOS sequence, Lys732LysLeu, critical for its CaM binding was also identified. Addition of CaM to inactive nNOS, generated by mutation of (Lys732LysLeu) to (Asp732AspGlu), which maintains dimerization ability, resulted in no enzyme activity, even at a 30:1 molar excess of CaM. Since dimerization is necessary for the activation of the native NOS enzyme, application of a dominant negative mutant through NOS assembly might be a useful biochemical approach in terms of elucidating NOS function in site.
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  • Masayuki UCHIDA, Kei MATSUEDA, Yumi KATO, Ryousuke SHODA, Shigeru YAMA ...
    1997 Volume 110 Issue 2 Pages 77-82
    Published: 1997
    Released on J-STAGE: January 30, 2007
    JOURNAL FREE ACCESS
    To clarify the mechanism of castor oil-induced diarrhea, this study was performed by using rats in relation to nitric oxide (NO) and prostaglandin (PG). Castor oil induced diarrhea in all rats within 3 hr in the control group. The pretreatment of NG-nitro-L-arginine methyl ester prevented the diarrhea, and this effect was attenuated by the combined treatment of L-arginine. Aminoguanidine inhibiting inducible NO synthase had no effect on the diarrhea, but dexamethasone, an inhibitor of both inducible NO synthase and phospholipase A2 that synthesizes PGs, significantly prevented it. Indomethacin, an inhibitor of cyclooxygenase that synthesizes PGs, also significantly prevented diarrhea. Therefore, the mechanism of the preventive effect by dexamethazone on diarrhea was suggested to be the inhibition of PGs generation. From the above results, it became clear that PG and NO, especially that synthesized by constitutive NO synthase, are involved in the mechanism of diarrhea induction by castor oil in rats.
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