Therapeutic Implications of Beta-Adrenergic Receptor Pharmacodynamic Properties

In the last decades new pharmacodynamic properties of beta-adrenoceptors have been discovered that could greatly impact in the use of beta-adrenergic agents in the clinical practice. Concepts such as multiple binding sites, constitutive activity, polymorphism and intracellular signaling of beta-adrenoceptors may contribute in the discovery of more efficacious pharmacological agents for treatment of heart failure and asthma. beta-Adrenoceptors show a relative high constitutive activity in both cardiac and pulmonar tissues. Most beta-blockers exert an inverse agonist action that could contribute to their beneficial effects in the treatment of heart failure. Recently, the existence of multiple affinity sites has been described for beta(1)-adrenoceptor. It was proposed that beta-blockers that show agonist properties at the beta(1L)-adrenoceptors binding site may exert neutral or harmful effects when used for treatment of heart failure. Considering the cardiac effect of beta(1L)-adrenoceptors, activation of the low-affinity state of beta(1)-adrenoceptor could be deleterous in cardiovascular pharmacology. The ability of beta(2)-adrenoceptor to couple to Gs or Gi-protein gives the possibility that different agonists can activate different signaling cascades. Full beta(2)-adrenoceptor agonists would be highly useful for improvement bronchodilatation in the acute treatment of asthma. Polymorphic variants of beta-adrenoceptors have profound impact in the understanding of normal physiology and pathophysiology. Genotypic characterization of patients could improve selection of patients during beta-adrenergic pharmacotherapies. The aim of the present review is to describe new insights in pharmacological and biochemical properties of beta-adrenoceptors and their impact on the use of beta-adrenergic agents in the treatment of cardiovascular and respiratory diseases.