Studies on the Mechanism of Action of the Gastric H^+,K^+-ATPase Inhibitor SPI-447

この論文にアクセスする

この論文をさがす

著者

    • ISHIKAWA Harumi
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • HIRASE Jyoji
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • NARITA Mitsuhiro
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • NISHIGAITO Toshiki
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • BANNO Kimiko
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • ICHIHARA Toshio
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc
    • TANAKA Hironori
    • Department of New Drug Research Laboratories, Technical Headquarters, Shinnippon Pharmaceutical, Inc

抄録

3−Amino−5−methyl−2(2−methyl−3−thienyl)−imidazo[1, 2−a]thieno[3, 2−c]pyridine, SPI−447, is a potent gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase inhibitor, but a detailed mechanism of the inhibition is unknown.This study was designed to investigate the mechanism by which SPI−447 inhibits gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase.For this purpose, the inhibitory action of SPI−447 on gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase from porcine gastric mucosa was compared with that of omeprazole(an irreversible inhibitor)and SCH28080(a reversible inhibitor).All compounds produced dose−dependent inhibition of gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase, and the inhibitory intensities were increased under acidic conditions.The anti−H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase actions of SPI−447 and SCH28080 were attenuated by dilution, but not influenced by glutathione pretreatment.In contrast, that of omeprazole was not influenced by dilution, but was suppressed by glutathione pretreatment.KCl addition reversed the inhibition of H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase−mediated H<SUP>+</SUP>−transport by SPI−447 and SCH28080, but had no effect on that by omeprazole.The anti−gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase action of SPI−447 was additive with that of SCH28080.SPI−447 and SCH28080 had no effect on Na<SUP>+</SUP>, K<SUP>+</SUP>−ATPase activity.These findings indicated that the inhibitory mechanism of SPI−447 on gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase was similar to that of SCH28080, but different from that of omeprazole;i.e., 1)reversible, 2)SH−group independent, 3)K<SUP>+</SUP>−competitive, and 4)highly specific against gastric H<SUP>+</SUP>, K<SUP>+</SUP>−ATPase.

収録刊行物

  • The Japanese journal of pharmacology

    The Japanese journal of pharmacology 82(1), 21-28, 2000-01-01

    公益社団法人 日本薬理学会

参考文献:  28件中 1-28件 を表示

被引用文献:  1件中 1-1件 を表示

各種コード

  • NII論文ID(NAID)
    10008182549
  • NII書誌ID(NCID)
    AA00691188
  • 本文言語コード
    ENG
  • 資料種別
    ART
  • ISSN
    00215198
  • NDL 記事登録ID
    4966414
  • NDL 雑誌分類
    ZS51(科学技術--薬学)
  • NDL 請求記号
    Z53-D199
  • データ提供元
    CJP書誌  CJP引用  NDL  J-STAGE 
ページトップへ