書誌事項
- タイトル別名
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- Cyclic AMP-dependent and Cyclic AMP-independent Inotropic Actions of PDE Inhibitors in Guinea-Pig Ventricular Papillary Muscles
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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
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- 日本薬理学雑誌
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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
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- CRID
- 1390001204270796416
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- NII論文ID
- 10008631439
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- NII書誌ID
- AN00198335
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- ISSN
- 13478397
- 00155691
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- 本文言語コード
- ja
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- データソース種別
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- JaLC
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- 抄録ライセンスフラグ
- 使用不可