Calcium antagonists and calmodulin: effect of verapamil, nifedipine and diltiazem.
The effect of three calcium antagonists (verapamil, nifedipine and diltiazem) on the calcium-induced activation of phosphodiesterase (a calmodulin dependent process) was investigated. Therapeutically relevant concentrations of verapamil, nifedipine and diltiazem were used. In the presence of calmodulin, phosphodiesterase activity was stimulated by calcium in the range 4 X 10(-6)-2.5 X 10(-5) M. Diltiazem (10(-6) M), verapamil (10(-6) M) and nifedipine (10(-7) and 10(-6) M) had no influence on phosphodiesterase activity in the presence or absence of calmodulin at any concentration of calcium employed. By contrast trifluoroperazine abolished the Ca2+ activation of the phosphodiesterase enzyme. From this it is concluded that while the interaction of calcium antagonists with calmodulin may be of interest in the study of the mode of action of calmodulin, it probably does not contribute to their vasodilator activity.
D000818:Animals; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D002135:Calcium-Binding Proteins / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D002417:Cattle; D004110:Diltiazem / Q000494:pharmacology; D004789:Enzyme Activation / Q000187:drug effects; D066298:In Vitro Techniques; D009543:Nifedipine / Q000494:pharmacology; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D002121:Calcium Channel Blockers; D002135:Calcium-Binding Proteins; D002147:Calmodulin; D014700:Verapamil; D010727:Phosphoric Diester Hydrolases; D004110:Diltiazem; D009543:Nifedipine; D002118:Calcium