モルモット乳頭筋におけるPDE阻害薬の特異的作用と非特異的作用

書誌事項

タイトル別名
  • Cyclic AMP-dependent and Cyclic AMP-independent Inotropic Actions of PDE Inhibitors in Guinea-Pig Ventricular Papillary Muscles

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抄録

The inotropic actions of xanthine derivatives, having long alkyl chains, were investigated in guinea-pig ventricular papillary muscle. A potent and nonselective phosphodiesterase (PDE) inhibitor, 3-isobutyl-l-methylxanthine, elicited a positive inotropy and inhibited the negative inotropic effects of calcium channel inhibitors, as well as a selective PDE III inhibitor, amrinone, these effects which were canceled by a protein kinase inhibitor, N-[2-(ρ-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide (H-89). However, 1, 3-di-n-butyl-7-(2'-oxopropyl)xanthine (denbufylline) and 1-n-butyl-3-n-propylxanthine (XT-044), which possess potent and selective PDE IV inhibitory activities, showed negative inotropic actions which became more potent in the presence of H-89. Denbufylline allowed to disappear late restoration phase induced by ryanodine. This xanthine derivative attenuated the both effects of calcium channel acting agents, Bay K 8644 and verapamil, without interaction with caffeine and dihydropyridine calcium channel inhibitors. A nonxanthine PDE IV inhibitor, Ro 20-1724, did not affect the inotropic actions of calcium channel inhibitors. The attenuation by denbufylline or XT-044 of the negative inotropic action of verapamil was not influenced by pretreatment with H-89. These results suggest that these xanthine derivatives elicit negative inotropy through acting on a verapamil-sensitive site of calcium channel without involving of their PDE inhibitory activitiy, in the ventricular papillary muscle.

収録刊行物

  • 日本薬理学雑誌

    日本薬理学雑誌 106 (supplement), 182-186, 1995

    公益社団法人 日本薬理学会

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詳細情報

  • CRID
    1390001204270796416
  • NII論文ID
    10008631439
  • NII書誌ID
    AN00198335
  • DOI
    10.1254/fpj.106.supplement_182
  • ISSN
    13478397
    00155691
  • 本文言語コード
    ja
  • データソース種別
    • JaLC
    • Crossref
    • CiNii Articles
  • 抄録ライセンスフラグ
    使用不可

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