Redox and proteolytic regulation of cardiomyocyte β1-adrenergic receptors - a novel paradigm for the regulation of catecholamine responsiveness in the heart

Conventional models view beta(1)-adrenergic receptors (beta(1)ARs) as full-length proteins that activate signaling pathways that influence contractile function and ventricular remodeling - and are susceptible to agonist-dependent desensitization. This perspective summarizes recent studies from my laboratory showing that post-translational processing of the beta(1)-adrenergic receptor N-terminus results in the accumulation of both full-length and N-terminally truncated forms of the beta(1)AR that differ in their signaling properties. We also implicate oxidative stress and beta(1)AR cleavage by elastase as two novel mechanisms that would (in the setting of cardiac injury or inflammation) lead to altered or decreased beta(1)AR responsiveness.