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

Abstract

The α1-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 β and α2-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 α1-AR subtypes (α1A, α1B, α1C) 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.

Adrenergic receptor signaling induced by Klf15, a regulator of regeneration enhancer, promotes kidney reconstruction

“…The adra1a and sap25 genes, which were identified as the direct targets of Klf15, may have active roles in the nephric tubule regeneration. Since agonists and antagonists for Adra1a are well characterized, we, therefore, decided to test whether adrenergic receptor contributes to regeneration of nephric tubules ( 28 ). Prazosin is a selective blocker for alpha-1 adrenergic receptor and has been previously applied to zebrafish ( 28 , 29 ).…”

“…Since agonists and antagonists for Adra1a are well characterized, we, therefore, decided to test whether adrenergic receptor contributes to regeneration of nephric tubules ( 28 ). Prazosin is a selective blocker for alpha-1 adrenergic receptor and has been previously applied to zebrafish ( 28 , 29 ). We injured the nephric tubules of transgenic Xenopus tadpoles ( Xla.Tg(Xtr.pax8:GFP) ) at stage 37 and treated them with 0.04 mg/mL prazosin, which resulted in inhibition of the nephric tubule regeneration ( Fig.…”

“…ARs are G protein coupled receptors that bind endogenous epinephrine, norepinephrine, and catecholamines. The biological function of adrenergic receptors is well known in regulating the sympathetic nervous system ( 28 ). In addition, previous studies show that stress-induced local epinephrine delays wound healing through the β2-AR ( 33 , 34 ).…”

Medikamentöse Behandlung des benignen Prostatasyndroms: Was gibt’s Neues?

“…Vor 3 Jahren schlug es ein wie eine Bombe: In der Analyse einer großen Datenbank aus den USA war die Einnahme des weltweit am häufigsten verschriebenen α-Blockers Tamsulosin relativ zu gematchten Männern ohne BPS Diagnose assoziiert mit einer moderaten Erhöhung des Risikos innerhalb von knapp 2 Jahren eine Demenzdiagnose zu erhalten (31,3 vs. 25,9 Fälle pro 1000 Personenjahre, relatives Risiko (RR) 1,17 [Konfidenzintervall 1,14 -1,21]); für andere α-Blocker wie Alfuzosin, Doxazosin oder Terazosin oder für die ARIs fand sich eine solche Assoziation nicht [5]. Dieser Befund ist ernst zu nehmen, weil es experimentelle Befunde gibt, nach denen Stimulation von α 1A -Adrenozeptoren im Gehirn einen anti-dementiven Effekt haben könnte [6]. Mechanistisch aber nur schwer verständlich ist, dass eine Wirkung auf die Kognition spezifisch für Tamsulosin sein soll: alle α-Blocker hemmen in therapeutischen Dosen den α 1A -Adrenozeptor, und Tamsulosin scheint im Vergleich zu anderen α-Blockern die schlechteste Penetration durch die Blut-Hirn-Schranke aufzuweisen [7].…”

Editorial: Cell Biology, Physiology and Molecular Pharmacology of G Protein Coupled Receptors

“…The collection of articles highlights the role of GPCRs in physiology, pathophysiology, and explores the possibility of exploiting their therapeutic potential. Perez (2021) reviews current developments on the role of α1-Adrenergic Receptors (α1-ARs) in cognition, cardioprotection, and metabolism. α1-ARs belong to the family of adrenergic receptors and have been extensively studied for their role in blood pressure regulation, cardiac hypertrophy, and muscle contraction.…”