β-adrenoceptors in cardiovascular and respiratory diseases

FUTURE PERSPECTIVES OVERVIEW β-Adrenoceptors (βARs) of which there are three subtypes (β1, β2 and β3) belong to the superfamily of seven transmembrane-spanning receptors or G protein-coupled receptors (GPCRs) and are the binding sites triggering the physiological actions of the catecholamine neurotransmitters, epinephrine and norepinephrine. Classically, the actions of catecholamines via βAR stimulation occur following activation of heterotrimeric G proteins and subsequent intracellular signal transduction pathways. βARs play a profound role in cardiovascular and pulmonary function because they are highly expressed on cardiac, vascular smooth muscle, and airway smooth muscle cells. This chapter will highlight the latest translational research that has recently provided important insight into how normal and abnormal βAR signaling can impact the cardiovascular and respiratory systems, including how mutations of these receptors, present in the human population, impact health and disease. INTRODUCTION β-adrenoceptors receptors (βARs) have been extensively studied in the last forty years. Genetic and molecular studies have confirmed three subtypes (β1-, β2- and β3-) based on their structure and function as well as tissue localization. Discoveries of the mechanisms governing βAR signaling has allowed development of therapeutic strategies to combat cardiovascular and respiratory diseases including βAR antagonists for hypertension and heart failure and selective β2AR agonists for asthma and airway disease. Further, targeting specific regulation of these receptors may lead to future novel therapeutic strategies for heart and pulmonary diseases.

Duke Scholars

Author Walter J. Koch Surgery, Cardiovascular and Thoracic Surgery