PMID: 11206708Feb 24, 2001Paper

Interaction between the partially insurmountable antagonist valsartan and human recombinant angiotensin II type 1 receptors

Fundamental & Clinical Pharmacology
Ilse VerheijenPatrick Vanderheyden

Abstract

The interaction between the AT1 receptor-selective antagonist valsartan, and its human receptor, was investigated by direct radioligand binding as well as by its inhibition of angiotensin II induced inositol phosphate accumulation in CHO cells expressing human recombinant AT1 receptors. Specific binding of [3H]-valsartan rapidly reached equilibrium at 37 degrees C. It was saturable and occurred to a homogeneous class of sites with a K(D) of 0.88+/-0.076. It was inhibited by other AT1 receptor antagonists with the same potency order as previously described for the binding of [3H]-angiotensin II and [3H]-candesartan to human AT1 receptors (i.e. candesartan > or = EXP3174 > valsartan = irbesartan = angiotensin II > losartan). When valsartan and angiotensin II were applied simultaneously to the CHO-AT1 cells. the antagonist caused a rightward shift of the angiotensin II concentration response curve. Hence, valsartan interacts with the AT1 receptor in a manner that is competitive with angiotensin II. Pre-incubation of the cells with 0.5, 5 and 50 nM valsartan caused an additional, concentration-dependent, up to 55% decline of the maximal response. The partial nature of this insurmountable inhibition by valsartan was confirmed by bip...Continue Reading

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Citations

Dec 6, 2006·European Journal of Clinical Pharmacology·Hyeong-Seok LimSang-Goo Shin
Sep 18, 2002·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Feb 27, 2007·Vascular Health and Risk Management·Bodh I Jugdutt
Nov 28, 2002·European Journal of Heart Failure·Emil PantevMalin Malmsjö
Mar 31, 2006·Kidney International·M A D H Schalekamp, A H J Danser
Jul 16, 2008·Molecular and Cellular Endocrinology·I Van Liefde, G Vauquelin
Apr 29, 2005·International Journal of Clinical Practice·L R Erhardt
Jan 26, 2016·British Journal of Pharmacology·Georges VauquelinDavid C Swinney
Jun 27, 2017·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Takanobu TakezakoKoichi Node
Mar 20, 2004·Expert Review of Cardiovascular Therapy·Steven G Chrysant
Feb 24, 2006·International Journal of Clinical Practice·R Asmar
Apr 8, 2006·Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension·Georges VauquelinIsabelle Van Liefde
Feb 13, 2014·British Journal of Pharmacology·Stephen P H AlexanderUNKNOWN CGTP Collaborators
Jun 19, 2007·The Journal of Pharmacology and Experimental Therapeutics·Erik LindströmGeorges Vauquelin
Feb 7, 2003·Fundamental & Clinical Pharmacology·G VauquelinP M L Vanderheyden
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde

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