β-Adrenergic receptor stimulation and activation of protein kinase A protect against α1-adrenergic-mediated phosphorylation of protein kinase D and histone deacetylase 5

These data indicate that the PKA-dependent arm of β-AR signaling can be antihypertrophic and presumably beneficial, through dephosphorylation of PKD and HDAC5 and reduction of hypertrophic fetal isoform gene expression.

Neonatal rat ventricular myocytes were acutely (15 minutes) or chronically (48 hours) treated with isoproterenol, and phosphorylation of protein kinase D (PKD) and histone deacetylase 5 (HDAC5) was measured. Acute β(1)-AR stimulation or expression of constitutively active (CA) PKA reduced α(1)-adrenergic-mediated phosphorylation of HDAC5 and PKD by activation of a phosphatase. Overexpression of CA-PKA also reduced α(1)-adrenergic-mediated increased expression of contractile protein fetal isoforms and promoted repression of adult isoforms, but had no effect on α(1)-adrenergic-mediated cellular hypertrophy. Conclusions: These data indicate that the PKA-dependent arm of β-AR signaling can be antihypertrophic and presumably beneficial, through dephosphorylation of PKD and HDAC5 and reduction of hypertrophic fetal isoform gene expression.