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 Ser16)-, 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-adrenoceptor 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 a. 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.
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 Ser16)-, 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-adrenoceptor 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 a. 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.
Authors: Bat-Erdene Myagmar; James M Flynn; Patrick M Cowley; Philip M Swigart; Megan D Montgomery; Kevin Thai; Divya Nair; Rumita Gupta; David X Deng; Chihiro Hosoda; Simon Melov; Anthony J Baker; Paul C Simpson Journal: Circ Res Date: 2017-02-20 Impact factor: 17.367
Authors: Peter Molenaar; Santiyagu M Savarimuthu; Doreen Sarsero; Lu Chen; Annalese B T Semmler; Anne Carle; Ian Yang; Sabine Bartel; Donate Vetter; Inge Beyerdörfer; Ernst-Georg Krause; Alberto J Kaumann Journal: Naunyn Schmiedebergs Arch Pharmacol Date: 2007-02-13 Impact factor: 3.000
Authors: Di Lang; Katherine Holzem; Chaoyi Kang; Mengqian Xiao; Hye Jin Hwang; Gregory A Ewald; Kathryn A Yamada; Igor R Efimov Journal: Circ Arrhythm Electrophysiol Date: 2015-02-11