Effects of Trifluoperazine on β‐Adrenergic Responses of Rat Papillary Muscle: Related to Calmodulin?

Abstract

The P-adrenergic stimulation of cardiac contraction and relaxation is related to an augmented Ca" oscillation mediated by CAMP. This Cat+ mobilization may secondarily involve calmodulin in a way modulating the mechanical responses. We tested this possibility by studying interferences of trifluoperazine (which is able to block Caw-calmodulin) with P-adrenergic responses in rat heart papillary muscles. Trifluoperazine up to Ic5 mol/l did not change the basal function.mol/l trifluoperazine augmented the contractile response to isoprenaline above lo' mol/l. The inotropic effects of isoprenaline below 16' mol/l and of the partial P-agonist prenalterol were not influenced by trifluoperazine. mol/l trifluoperazine attenuated the stimulation of initial relaxation by isoprenaline in the entire concentration range. Thus this P-adrenergic response was more sensitive to trifluoperazine than the contractile response. But trifluoperazine only slightly and non-significantly attenuated the stimulation of initial relaxation by prenalterol. From experiments on broken cell preparations the present results can be explained in terms of calmodulin blockade and thus inhibition of Cat+ efflux across the sarcolemma and of Ca" uptake by the sarcoplasmic reticulum. Trifluoperazine effects unrelated to calmodulin can hardly account for the results. Thus a full P-agonist can apparently mobilize enough Ca" to activate calmodulin systems important for the final effects on the contraction-relaxation cycle.