日本薬理学雑誌
Online ISSN : 1347-8397
Print ISSN : 0015-5691
ISSN-L : 0015-5691
110 巻, 2 号
選択された号の論文の4件中1~4を表示しています
  • 米田 幸雄, 荻田 喜代一
    1997 年 110 巻 2 号 p. 45-57
    発行日: 1997年
    公開日: 2007/01/30
    ジャーナル フリー
    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.
  • 大石 幸子
    1997 年 110 巻 2 号 p. 59-68
    発行日: 1997年
    公開日: 2007/01/30
    ジャーナル フリー
    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.
  • 渡辺 泰男
    1997 年 110 巻 2 号 p. 69-75
    発行日: 1997年
    公開日: 2007/01/30
    ジャーナル フリー
    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.
  • 内田 勝幸, 松枝 啓, 加藤 由美, 正田 良介, 大和 滋, 村岡 亮
    1997 年 110 巻 2 号 p. 77-82
    発行日: 1997年
    公開日: 2007/01/30
    ジャーナル フリー
    ヒマシ油の下痢発現機序を検討する目的で一酸化窒素(NO)およびプロスタグランジン(PG)との関与についてラットを用いて検討した.ヒマシ油をラットに経口投与すると3時間以内に下痢が誘起された.NO合成酵素阻害薬であるNG-ニトロ-L-アルギニンメチルエステルを前処置することによりヒマシ油の下痢は有意に抑制され,レアルギニンの併用投与により回復した。誘導型NO合成酵素阻害薬であるアミノグアニジンの前処置は下痢に影響を及ぼさなかったが,誘導型NO合成酵素阻害作用とPG合成酵素であるボスホリパーゼA2阻害作用の両作用をもつデキサメサゾンの前処置は下痢を有意に抑制した.また,PG合成酵素であるシクロオキシゲナーゼの阻害薬であるインドメタシンの前処置も下痢を有意に抑制した.したがって,デキサメサゾンの下痢抑制作用はPG合成酵素であるボスホリパーゼA2阻害によるPG合成阻害作用によるものと考えられた.以上のことから,ヒマシ油の下痢の発現機序に構成型のNO合成酵素によるNOとPGの両者が関与していることが明らかになった.
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