Current Developments on the Role of α1-Adrenergic Receptors in Cognition, Cardioprotection, and Metabolism

The alpha(1)-adrenergic receptors (ARs) are G-protein coupled receptors that bind the endogenous catecholamines, norepinephrine, and epinephrine. They play a key role in the regulation of the sympathetic nervous system along with beta and alpha(2)-AR family members. While all of the adrenergic receptors bind with similar affinity to the catecholamines, they can regulate different physiologies and pathophysiologies in the body because they couple to different G-proteins and signal transduction pathways, commonly in opposition to one another. While alpha(1)-AR subtypes (alpha(1A), alpha(1B), alpha(1C)) have long been known to be primary regulators of vascular smooth muscle contraction, blood pressure, and cardiac hypertrophy, their role in neurotransmission, improving cognition, protecting the heart during ischemia and failure, and regulating whole body and organ metabolism are not well known and are more recent developments. These advancements have been made possible through the development of transgenic and knockout mouse models and more selective ligands to advance their research. Here, we will review the recent literature to provide new insights into these physiological functions and possible use as a therapeutic target.

Automated summary

Alpha(1)-adrenergic receptors play various roles in the body beyond regulating vascular smooth muscle contraction and blood pressure, including neurotransmission, cognition, and cardiac protection. Advances in research using transgenic and knockout mouse models, as well as more selective ligands, have provided deeper insights into their physiological functions.