New insights into β2-adrenoceptor signaling in the adult rat heart

Objective: The role of cAMP in beta(2)-adrenoceptor signaling and its functional relevance in adult rat heart has been the Subject of considerable controversy. Therefore, we investigated the beta(2)-adrenoceptor pathways in both adult cardiomyocytes and in the intact hearts of Wistar rats with respect to protein kinase A (at Sei-16)-, the key event in shortening of relaxation time, and CaM kinase II (at Thr17)-dependent phospholamban phosphorylation. Methods: Contractile and Cellular beta(1)/beta(2)-adrenergic responses were studied in parallel on the same perfused rat heart. (-)Isoproterenol and the beta(2)-adrenergic agonists zinterol and procaterol were used to discriminate the beta-adrcnoceptor subtype-related actions. Results: beta(2)-Adrenoceptor stimulation induces protein kinase A-dependent phospholamban phosphorylation in both adult cardiomyocytes and in adult hearts of rats. The beta(2)-adrenoceptor-mediated shortening of relaxation time in the heart correlates with Ser16 phosphorylation. Adenosine elicited antiadrenergic action on both beta(1)- and beta(2)-adrenergic signaling cascades by reducing the phosphorylation Status of phospholamban. Only beta(1)-adrenoceptor stimulation produced significant CaM kinase II-related Thr17 phosphorylation. troponin I phosphorylation and activation of phosphorylase. Conclusions: Our findings clearly show that beta(2)-adrenoceptor signaling is coupled to phospholamban phosphorylation and shortening of relaxation time in the adult rat heart. (C) 2003 European Society of Cardiology. Published by Elsevier Science B.V. All rights reserved.