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New insights into beta2 adrenoceptor signaling in the adult rat heart

Item Type:Article
Title:New insights into beta2 adrenoceptor signaling in the adult rat heart
Creators Name:Bartel, S. and Krause, E.G. and Wallukat, G. and Karczewski, P.
Abstract: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.
Keywords:Adrenergic (ant)agonists, Myocytes, Receptors, Signal Transduction, Animals, Rats
Source:Cardiovascular Research
Page Range:694-703
Date:1 March 2003
Official Publication:https://doi.org/10.1016/S0008-6363(02)00720-4
PubMed:View item in PubMed

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