Distinct binding properties of the AT(1) receptor antagonist [(3)H]candesartan to intact cells and membrane preparations

Biochemical Pharmacology
F L FierensG Vauquelin

Abstract

[(3)H]-2-Ethoxy-1-[(2'-(1H-tetrazol-5-yl)biphenyl-4-yl)methyl]-1H-benzimidazoline-7-carboxylic acid ([(3)H]candesartan), a non-peptide angiotensin II type 1 receptor (AT(1) receptor) antagonist bound with high affinity and specificity to intact adherent human AT(1) receptor transfected Chinese hamster ovary cells. The binding characteristics were preserved when cells were suspended, but the dissociation was 3-4-fold faster and the affinity 2-fold lower, while examining [(3)H]candesartan binding to cell membranes. These data suggested the role of the intracellular organisation of living CHO-hAT(1) cells in antagonist-AT(1) receptor interactions. Yet, a specific role of microtubule or actin filaments of the cytoskeleton, receptor phosphorylation by Protein Kinase C, membrane polarity, cytoplasmic components like ATP and the need of an intact cell membrane could be excluded. The potential effect of protease degradation or receptor oxidation during the membrane preparation was also unlikely. The dissociation rate and the equilibrium dissociation constant of [(3)H]candesartan increased with the temperature for both intact cells and membranes. Thermodynamic studies suggested that the bonds between candesartan and the hAT(1) receptor ...Continue Reading

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Citations

Feb 15, 2012·Naunyn-Schmiedeberg's Archives of Pharmacology·Georges VauquelinPhilip Seeman
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde
May 3, 2016·British Journal of Clinical Pharmacology·Georges Vauquelin
Jan 3, 2016·Drug Discovery Today. Technologies·Georges VauquelinDavid C Swinney
Oct 1, 2010·British Journal of Pharmacology·Georges Vauquelin, Steven J Charlton
Jan 26, 2016·British Journal of Pharmacology·Georges VauquelinDavid C Swinney
Aug 26, 2009·Fundamental & Clinical Pharmacology·M WennerbergGeorges Vauquelin
Dec 18, 2009·Fundamental & Clinical Pharmacology·Ann PackeuGeorges Vauquelin
Apr 8, 2006·Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension·Georges VauquelinIsabelle Van Liefde
Feb 24, 2012·The Journal of Pharmacology and Experimental Therapeutics·Beth A FleckDimitri E Grigoriadis
Jul 9, 2010·Fundamental & Clinical Pharmacology·Marie WennerbergGeorges Vauquelin
Dec 13, 2019·Biochimica Et Biophysica Acta. Biomembranes·Sofia KiriakidiThomas Mavromoustakos
Feb 5, 2013·European Journal of Pharmacology·Alexandros NikolaouPatrick M L Vanderheyden
Mar 26, 2004·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Apr 26, 2008·Biochemical Pharmacology·Ann PackeuGeorges Vauquelin
Aug 4, 2009·Molecular and Cellular Endocrinology·G Vauquelin, A Packeu

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