A xanthine derivative denbufylline inhibits negative inotropic response to verapamil in guinea pig ventricular papillary muscles, independent of its phosphodiesterase inhibitory activity.
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.
Sanae
F
F
Department of Applied Pharmacology, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Ohmae
S
S
Takagi
K
K
Miyamoto
K
K
D000818:Animals; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D006321:Heart / Q000187:drug effects*; D008297:Male; D009529:Nicardipine / Q000494:pharmacology; D010726:Phosphodiesterase Inhibitors / Q000494:pharmacology*; D014700:Verapamil / Q000494:pharmacology*; D014970:Xanthines / Q000494:pharmacology*
D010726:Phosphodiesterase Inhibitors; D014970:Xanthines; C043898:denbufylline; D014700:Verapamil; D009529:Nicardipine