Antagonist interaction with endogenous AT(1) receptors in human cell lines

Biochemical Pharmacology
Ilse VerheijenGeorges Vauquelin


Using Chinese Hamster Ovary cells expressing human AT(1) receptors cells (CHO-hAT(1)), it was previously shown that insurmountable inhibition of the angiotensin II response by non-peptide antagonists is related to the duration of their receptor occupancy. In the present study it was shown that these antagonists displayed similar binding characteristics to endogenously expressed AT(1) receptors in human adrenal cortex cells (NCI-h295) and renal vascular smooth muscle cells (HVSMC). Competition binding studies with [(3)H]candesartan for NCI-h295 cells, with [(125)I]Sar(1)-Ile(8) angiotensin II for HVSMC and with both radioligands for CHO-hAT(1) cells displayed the same potency order for unlabelled antagonists: candesartan>EXP3174>irbesartan>losartan. The AT(2) receptor antagonist PD123319 displayed low potency in all instances. The apparent half-lives of the antagonist-AT(1) receptor complexes in NCI-h295 cells and HVSMC were comparable to those obtained under identical conditions with CHO-hAT(1) cells. Angiotensin II increased the inositol phosphate accumulation dose dependently with half-maximal response at 17.4+/-1.6nM for NCI-h295 cells and 4.5+/-0.8nM for HVSMC. Pre-incubation of the cells with losartan only produced concent...Continue Reading


Jun 19, 1991·European Journal of Pharmacology·S P BottariM de Gasparo
Jan 1, 1995·Journal of Cardiovascular Pharmacology·S MochizukiA Tomiyama
Mar 25, 1998·Biophysical Journal·B C Lagerholm, N L Thompson
Jul 8, 1999·European Journal of Pharmacology·F L FierensG Vauquelin
Apr 23, 2002·Journal of the Renin-angiotensin-aldosterone System : JRAAS·P M VanderheydenG Vauquelin

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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
Apr 26, 2008·Biochemical Pharmacology·Ann PackeuGeorges Vauquelin

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