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New insights into beta2-adrenoceptor signaling in the adult rat heart.
- Source :
-
Cardiovascular research [Cardiovasc Res] 2003 Mar; Vol. 57 (3), pp. 694-703. - Publication Year :
- 2003
-
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.<br />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.<br />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.<br />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.
- Subjects :
- Adenosine pharmacology
Adrenergic beta-Agonists pharmacology
Animals
Calcium-Binding Proteins metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases physiology
Calcium-Transporting ATPases physiology
Cells, Cultured
Cyclic AMP metabolism
Cyclic AMP-Dependent Protein Kinases metabolism
Ethanolamines pharmacology
Male
Muscle Cells physiology
Muscle Contraction drug effects
Phosphorylase a metabolism
Phosphorylation
Rats
Rats, Wistar
Troponin I metabolism
Heart physiology
Receptors, Adrenergic, beta physiology
Signal Transduction physiology
Subjects
Details
- Language :
- English
- ISSN :
- 0008-6363
- Volume :
- 57
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Cardiovascular research
- Publication Type :
- Academic Journal
- Accession number :
- 12618231
- Full Text :
- https://doi.org/10.1016/s0008-6363(02)00720-4