Differential phosphorylation, desensitization, and internalization of α1A-adrenoceptors activated by norepinephrine and oxymetazoline

Molecular Pharmacology
Juliana AkinagaAndré Sampaio Pupo

Abstract

Loss of response on repetitive drug exposure (i.e., tachyphylaxis) is a particular problem for the vasoconstrictor effects of medications containing oxymetazoline (OXY), an α1-adrenoceptor (AR) agonist of the imidazoline class. One cause of tachyphylaxis is receptor desensitization, usually accompanied by phosphorylation and internalization. It is well established that α1A-ARs are less phosphorylated, desensitized, and internalized on exposure to the phenethylamines norepinephrine (NE), epinephrine, or phenylephrine (PE) than are the α1B and α1D subtypes. However, here we show in human embryonic kidney-293 cells that the low-efficacy agonist OXY induces G protein-coupled receptor kinase 2-dependent α1A-AR phosphorylation, followed by rapid desensitization and internalization (∼40% internalization after 5 minutes of stimulation), whereas phosphorylation of α1A-ARs exposed to NE depends to a large extent on protein kinase C activity and is not followed by desensitization, and the receptors undergo delayed internalization (∼35% after 60 minutes of stimulation). Native α1A-ARs from rat tail artery and vas deferens are also desensitized by OXY, but not by NE or PE, indicating that this property of OXY is not limited to recombinant r...Continue Reading

References

Jun 1, 1977·The Journal of Pharmacy and Pharmacology·R R RuffoloP N Patil
Feb 28, 1994·Biochemical and Biophysical Research Communications·M GschwendtF Marks
Aug 1, 1998·European Journal of Pharmacology·A S Pupo
Feb 29, 2000·The Journal of Biological Chemistry·J Vázquez-PradoJ A García-Sáinz
Sep 22, 2000·The Biochemical Journal·S P DaviesP Cohen
Jun 18, 2002·The Journal of Pharmacology and Experimental Therapeutics·Aleksandra VicenticKenneth P Minneman
Feb 20, 2003·European Journal of Pharmacology·Andre S PupoKenneth P Minneman
Jul 8, 2003·Naunyn-Schmiedeberg's Archives of Pharmacology·Marcelo CamposAndré S Pupo
Dec 6, 2003·Pharmacological Reviews·Richard R NeubigUNKNOWN International Union of Pharmacology Committee on Receptor Nomenclature and Drug Classification
Jan 14, 2004·The Journal of Pharmacology and Experimental Therapeutics·Chris HagueKenneth P Minneman
May 8, 2004·Biochemical Pharmacology·J Adolfo García-SáinzM Teresa Romero-Avila
Sep 17, 2004·The Biochemical Journal·S Eréndira Avendaño-VázquezJ Adolfo García-Sáinz
May 6, 2005·The Journal of Pharmacology and Experimental Therapeutics·Susana Y KamikiharaAndré S Pupo
Oct 18, 2005·Acta Pharmacologica Sinica·Zhong-jian Chen, Kenneth P Minneman
May 10, 2006·Molecular Pharmacology·Elizabeth A JohnsonGraeme Henderson
Jul 3, 2007·British Journal of Pharmacology·A SanbeA Tanoue
Sep 14, 2007·The Biochemical Journal·Jenny BainPhilip Cohen
Jun 6, 2009·Proceedings of the National Academy of Sciences of the United States of America·David A ZidarRobert J Lefkowitz
Oct 29, 2009·Cellular and Molecular Life Sciences : CMLS·James R Docherty
Mar 6, 2010·American Journal of Respiratory and Critical Care Medicine·Sriram VaidyanathanBrian Lipworth
Oct 6, 2010·Naunyn-Schmiedeberg's Archives of Pharmacology·Alejandro Cabrera-WroomanJ Adolfo García-Sáinz
Oct 20, 2010·Journal of Receptor and Signal Transduction Research·Susanna Cotecchia
Oct 28, 2010·Molecular Pharmacology·Bronwyn A EvansRoger J Summers
Feb 23, 2011·Journal of Receptor and Signal Transduction Research·Dianne M Perez, Van A Doze
Apr 1, 2011·British Journal of Pharmacology·Christian DollStefan Schulz
Sep 29, 2011·Annual Review of Pharmacology and Toxicology·Eric ReiterRobert J Lefkowitz
Feb 3, 2012·Sleep Medicine Reviews·Craig W BerridgeRodrigo A España
Mar 1, 2012·The Journal of Biological Chemistry·Sanam MustafaKevin D G Pfleger
Jun 26, 2012·British Journal of Pharmacology·Christian DollStefan Schulz

❮ Previous
Next ❯

Citations

Apr 23, 2014·Archives of Medical Research·Jean A Castillo-BadilloJ Adolfo García-Sáinz
Oct 16, 2015·Bulletin of Experimental Biology and Medicine·M V VasinV V Antipov
Dec 28, 2016·International Journal of Molecular Sciences·Marco A Alfonzo-MéndezJ Adolfo García-Sáinz
Mar 28, 2019·Pharmacological Reviews·Terry Kenakin
Apr 2, 2020·Bioelectronic Medicine·Andrea Stofkova, Masaaki Murakami
Jul 10, 2019·The Journal of Pharmacology and Experimental Therapeutics·Bruna Maria Castro Salomão QuaresmaFrançois Noël
Sep 22, 2019·Seminars in Cardiothoracic and Vascular Anesthesia·Patrick J ColemanJonathan H Chow
Oct 25, 2014·Journal of Applied Physiology·Jody L GreaneyLacy M Alexander
Aug 21, 2019·Circulation Research·Bat-Erdene MyagmarPaul C Simpson
Apr 1, 2020·Journal of Intensive Care Medicine·Mojdeh S HeavnerJonathan H Chow
Aug 5, 2020·European Journal of Pharmacology·Gustavo de-Los-Santos-CocotleJ Adolfo García-Sáinz
Mar 3, 2020·European Journal of Cell Biology·Rocío Alcántara-HernándezJ Adolfo García-Sáinz
Mar 30, 2021·Frontiers in Veterinary Science·Alexander Valverde
Sep 24, 2015·Disease Models & Mechanisms·María González-NúñezJose M López-Novoa
Jun 12, 2021·Frontiers in Cell and Developmental Biology·Dianne M Perez

❮ Previous
Next ❯

Related Concepts

Related Feeds

Adrenergic Receptors: Trafficking

Adrenergic receptor trafficking is an active physiological process where adrenergic receptors are relocated from one region of the cell to another or from one type of cell to another. Discover the latest research on adrenergic receptor trafficking here.