Insurmountable angiotensin AT1 receptor antagonists: the role of tight antagonist binding

European Journal of Pharmacology
F L FierensG Vauquelin

Abstract

Angiotensin II increased the inositol phosphates production (EC50 = 3.4+/-0.7 nM) in Chinese hamster ovary (CHO) cells expressing the cloned human angiotensin AT1 receptor (CHO-AT1 cells). Coincubation with angiotensin AT1 receptor antagonists produced parallel rightward shifts of the concentration-response curve without affecting the maximal response. The potency order is 2-ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benz imidazoline-7-carboxylic acid (candesartan) > 2-n-butyl-4-chloro-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]i midazole-5-carboxylic acid (EXP3174) > 2-n-butyl-4-spirocyclopentane-1-[(2'-(1H-tetrazol-5-yl)biphe nyl-4-yl)methyl]2-imidazolin-5-one (irbesartan)> of 2-n-butyl-4-chloro-5-hydroxymethyl-1-(2'-(1H-tetrazol-5-yl)bipheny l-4-yl)methyl]imidazole (losartan). Additionally, preincubation with these antagonists depressed the maximal response, i.e., 95%, 70%, 30% of the control response for candesartan, EXP3174 and irbesartan and not detectable for losartan. Increasing the antagonist concentration or prolonging the preincubation time did not affect this depression. Furthermore, these values remained constant for candesartan and EXP3174, when the angiotensin II incubation time varied between 1 ...Continue Reading

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Citations

Aug 14, 2001·Pharmazie in unserer Zeit·R Hübner, W Fuchs
Feb 15, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Georges VauquelinPhilip Seeman
Aug 12, 2005·European Journal of Clinical Pharmacology·Xiumei HongXiping Xu
Apr 27, 2001·Biochemical Pharmacology·F L FierensaG Vauquelin
Sep 18, 2002·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Mar 4, 2000·Lancet·M Burnier, H R Brunner
Oct 26, 2000·Trends in Pharmacological Sciences·M J LewA Christopoulos
Jul 20, 2001·Trends in Pharmacological Sciences·G VauquelinP Vanderheyden
Feb 7, 2003·Fundamental & Clinical Pharmacology·G VauquelinP M L Vanderheyden
Feb 15, 2005·International Journal of Clinical Practice·J-L ImbsUNKNOWN French Collaborative Candesartan Study Group
Sep 15, 2012·European Journal of Pharmacology·Nitya V JaniChristine E Wright
Dec 9, 2008·Molecular and Cellular Endocrinology·Hiroshi AkazawaIssei Komuro
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde
Feb 20, 2014·Medicinal Research Reviews·Dong GuoLaura H Heitman
Jan 5, 2002·Expert Opinion on Investigational Drugs·M WhiteJ de Champlain
Nov 3, 2004·Trends in Endocrinology and Metabolism : TEM·László Hunyady, Gábor Turu
Jun 8, 2001·Journal of Cardiovascular Pharmacology·M S BerlowitzT H Le Jemtel
Jul 26, 2002·Journal of Human Hypertension·A H Gradman
Feb 15, 2001·Circulation·M Burnier
Mar 1, 2001·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Georges VauquelinPatrick Ml Vanderheyden
Mar 1, 2001·Journal of the Renin-angiotensin-aldosterone System : JRAAS·Georges VauquelinPatrick Ml Vanderheyden
Oct 28, 2010·British Journal of Pharmacology·Steven J Charlton, Georges Vauquelin
Apr 8, 2006·Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension·Georges VauquelinIsabelle Van Liefde
Dec 3, 2010·The Journal of Pharmacology and Experimental Therapeutics·Mami OjimaHideaki Nagaya
Jun 19, 2007·The Journal of Pharmacology and Experimental Therapeutics·Erik LindströmGeorges Vauquelin
Aug 17, 2002·The Journal of Pharmacology and Experimental Therapeutics·Marc P MaillardMichel Burnier

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