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  [in Japanese] Cyclic AMP-dependent and Cyclic AMP-independent Inotropic Actions of PDE Inhibitors in Guinea-Pig Ventricular Papillary Muscles  [in Japanese]

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Author(s)

    • 宮本 謙一 MIYAMOTO Ken-ichi
    • 北陸大学薬学部薬効解析学教室 Faculty of Pharmaceutical Sciences, Hokuriku University, Department of Applied Pharmacology.
    • 大前 真司 OHMAE Shinji
    • 北陸大学薬学部薬効解析学教室 Faculty of Pharmaceutical Sciences, Hokuriku University, Department of Applied Pharmacology.
    • 早苗 富士子 SANAE Fujiko
    • 北陸大学薬学部薬効解析学教室 Faculty of Pharmaceutical Sciences, Hokuriku University, Department of Applied Pharmacology.
    • 高木 健三 TAKAGI Kenzo
    • 名古屋大学医学部第二内科学教室 Second Department of Internal Medicine, Nagoya University School of Mdicine

Abstract

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.

Journal

  • Folia Pharmacologica Japonica

    Folia Pharmacologica Japonica 106, 182-186, 1995-09-01

    The Japanese Pharmacological Society

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