Fujiko Sanae (1), Shinji Ohmae (1), Kenzo Takagi (2) and Ken-ichi Miyamoto (1,*)
(1) Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Ho-3 Kanagawa-machi, Kanazawa 920-11, Japan
(2) Second Department of Internal Medicine, Nagoya University School of Medicine, Tsurumai, Nagoya 466, Japan
(*) To whom correspondence should be addressed./I>
Abstract: A phosphodiesterase (PDE) III inhibitor, amrinone, inhibited both the negative inotropic actions of verapamil and nicardipine in guinea pig ventricular papillary muscle; this effect was canceled by the protein kinase A inhibitor H-89. The PDE IV inhibitor 1,3-di-n-butyl-7-(2'-oxopropyl)xanthine (denbufylline), which elicited a negative inotropic action by itself, attenuated the action of verapamil up to 10 microM, without any interaction with nicardipine. The attenuation by denbufylline was not influenced by H-89. This suggests that in the ventricular papillary muscle, denbufylline acts on some verapamil-sensitive site(s) in the membrane and interferes with the calcium channel function without involvement of its PDE inhibitory activity.
Keywords: Denbufylline, Negative inotropy, Calcium channel