Sartan-AT1 receptor interactions: in vitro evidence for insurmountable antagonism and inverse agonism

Molecular and Cellular Endocrinology
I Van Liefde, G Vauquelin

Abstract

Sartans are non-peptide AT(1) receptor antagonists used to treat hypertension and related pathologies. Their effects on the G protein-dependent responses of angiotensin II (Ang II) were the same in vascular tissues and in isolated cell systems. All are competitive but, when pre-incubated, they act surmountably (only rightward shift of the Ang II concentration-response curve) or insurmountably (also decreasing the maximal response). Insurmountable behaviour reflects the formation of tight sartan-receptor complexes; it is often partial due to the co-existence of tight and loose complexes. Their ratio positively correlates with the dissociation half-life of the tight complexes and depends on the sartan: i.e. candesartan>olmesartan>telmisartan approximately equal EXP3174>valsartan>irbesartan>losartan. When AT(1) receptors display sufficient basal activity (in case of receptor over-expression, mutation and, especially, tissue stretching) sartans may also act as inverse agonists. This rather affects long-term, G protein-independent hypertrophic responses leading to cardiovascular remodelling.

References

Jul 1, 1986·British Journal of Pharmacology·P Leff, G R Martin
Dec 1, 1995·The Journal of Biological Chemistry·K NodaS S Karnik
Aug 1, 1995·Circulation Research·T YamazakiK Tobe
Jul 1, 1995·The Journal of Clinical Investigation·T YamazakiK Tobe
Jan 1, 1995·Journal of Cardiovascular Pharmacology·S MochizukiA Tomiyama
Sep 16, 1999·Hypertension Research : Official Journal of the Japanese Society of Hypertension·P B Timmermans
Apr 23, 2002·Journal of the Renin-angiotensin-aldosterone System : JRAAS·P M VanderheydenG Vauquelin
Feb 1, 2003·Trends in Pharmacological Sciences·László HunyadyPatrick Vanderheyden
May 30, 2003·Journal of Medicinal Chemistry·Boris Schmidt, Bernhard Schieffer
Jan 14, 2004·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Shin-ichiro MiuraSadashiva S Karnik
Mar 20, 2004·Expert Review of Cardiovascular Therapy·Keith Norris, Charles Vaughn
Mar 26, 2004·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde
Jan 13, 2006·Journal of Molecular Modeling·Camelia Baleanu-Gogonea, Sadashiva Karnik
May 13, 2006·The Journal of Biological Chemistry·Shin-ichiro MiuraKeijiro Saku
Jun 13, 2006·Trends in Pharmacological Sciences·Georges Vauquelin, Isabelle Van Liefde
Feb 13, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Erol SaygiliCarsten Zobel
Jul 4, 2007·Neurochemistry International·Georges Vauquelin, Anna Szczuka

❮ Previous
Next ❯

Citations

Feb 23, 2010·Advances in Therapy·Roberto FogariGiuseppe Derosa
Aug 8, 2009·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Yingjie QinIssei Komuro
Oct 15, 2010·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Lei LiYunzeng Zou
May 11, 2012·Hypertension Research : Official Journal of the Japanese Society of Hypertension·Takuya KishiKenji Sunagawa
May 26, 2010·Clinical and Experimental Pharmacology & Physiology·Maria A SardoAntonino Saitta
Aug 10, 2011·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Yoshihiro KiyaKeijiro Saku
Jul 3, 2013·Biological & Pharmaceutical Bulletin·Yong Ha ChiKyung-Tae Lee
Nov 13, 2012·ClinicoEconomics and Outcomes Research : CEOR·Ola GranströmMartin Henriksson
Jan 14, 2012·Vascular Health and Risk Management·Relu CernesReuven Zimlichman
Mar 9, 2012·Vascular Health and Risk Management·Theodore W Kurtz, Takashi Kajiya
Oct 9, 2013·Pflügers Archiv : European journal of physiology·Stephanie BlodowMichael Mederos y Schnitzler
Nov 23, 2012·Expert Opinion on Pharmacotherapy·Amedeo Mugellini, Valentina Nieswandt
Sep 1, 2011·Expert Review of Cardiovascular Therapy·Zeeshan Khawaja, Christopher S Wilcox
Jul 1, 2009·Expert Opinion on Pharmacotherapy·B Mendis, S R Page
Jan 19, 2012·Clinical and Experimental Hypertension : CHE·Hiroshi HasegawaIssei Komuro
Sep 6, 2011·Bioorganic & Medicinal Chemistry Letters·Duncan C MillerAlan D Brown
Jul 23, 2011·Drug Discovery Today·Sara NúñezChris G Kruse
Jan 3, 2016·Drug Discovery Today. Technologies·Georges VauquelinDavid C Swinney
Dec 29, 2009·Journal of Pharmacological and Toxicological Methods·Pamela R TsurudaJacqueline A M Smith
Oct 1, 2010·British Journal of Pharmacology·Georges Vauquelin, Steven J Charlton
Jan 26, 2016·British Journal of Pharmacology·Georges VauquelinDavid C Swinney
Nov 19, 2013·International Journal of Cardiology·Hae Chang JeongUNKNOWN Korea Acute Myocardial Infarction Registry Investigators
Jul 27, 2015·European Journal of Medicinal Chemistry·Julien LouvelAdriaan P IJzerman
Jun 27, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takanobu TakezakoKoichi Node
Dec 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Mami OjimaHideaki Nagaya
Aug 14, 2019·Therapeutic Advances in Cardiovascular Disease·Uma MarkanAnastasios Lymperopoulos
Sep 14, 2010·American Journal of Physiology. Heart and Circulatory Physiology·A H Jan Danser
Jul 3, 2017·Naunyn-Schmiedeberg's Archives of Pharmacology·Juraj CulmanPeter Gohlke
Apr 17, 2020·ACS Pharmacology & Translational Science·Wijnand J C van der VeldenMette M Rosenkilde

❮ Previous
Next ❯

Related Concepts

Related Feeds

Cardiomyopathy

Cardiomyopathy is a disease of the heart muscle, that can lead to muscular or electrical dysfunction of the heart. It is often an irreversible disease that is associated with a poor prognosis. There are different causes and classifications of cardiomyopathies. Here are the latest discoveries pertaining to this disease.