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Crosstalk between adenosine A1 and beta1-adrenergic receptors regulates translocation of PKCepsilon in isolated rat cardiomyocytes.

Authors: Komatsu, S  Dobson JG, JR  Ikebe, M  Shea, LG  Fenton, RA 
Citation: Komatsu S, etal., J Cell Physiol. 2012 Sep;227(9):3201-7. doi: 10.1002/jcp.24008.
Pubmed: (View Article at PubMed) PMID:22105697
DOI: Full-text: DOI:10.1002/jcp.24008

Adenosine A(1) receptor (A(1)R)-induced translocation of PKCepsilon to transverse (t) tubular membranes in isolated rat cardiomyocytes is associated with a reduction in beta(1)-adrenergic-stimulated contractile function. The PKCepsilon-mediated activation of protein kinase D (PKD) by endothelin-1 is inhibited by beta(1)-adrenergic stimulated protein kinase A (PKA) suggesting a similar mechanism of A(1)R signal transduction modulation by adrenergic agonists may exist in the heart. We have investigated the influence of beta(1)-adrenergic stimulation on PKCepsilon translocation elicited by A(1)R. Immunofluorescence imaging and Western blotting with PKCepsilon and beta-COP antibodies were used to quantify the co-localization of PKCepsilon and t-tubular structures in isolated rat cardiomyocytes. The A(1)R agonist CCPA increased the co-localization of PKCepsilon and t-tubules as detected by imaging. The beta(1)-adrenergic receptor agonist isoproterenol (ISO) inhibited this effect of CCPA. Forskolin, a potent activator of PKA, mimicked, and H89, a pharmacological PKA inhibitor, and PKI, a membrane-permeable PKA peptide PKA inhibitor, attenuated the negative effect of ISO on the A(1)R-mediated PKCepsilon translocation. Western blotting with isolated intact hearts revealed an increase in PKCepsilon/beta-COP co-localization induced by A(1)R. This increase was attenuated by the A(1)R antagonist DPCPX and ISO. The ISO-induced attenuation was reversed by H89. It is concluded that adrenergic stimulation inhibits A(1)R-induced PKCepsilon translocation to the PKCepsilon anchor site RACK2 constituent of a coatomer containing beta-COP and associated with the t-tubular structures of the heart. In that this translocation has been previously associated with the antiadrenergic property of A(1)R, it is apparent that the interactive effects of adenosine and beta(1)-adrenergic agonists on function are complex in the heart.


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RGD Object Information
RGD ID: 6893637
Created: 2012-09-13
Species: All species
Last Modified: 2012-09-13
Status: ACTIVE


RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.