Binding characteristics of [(3)H]-irbesartan to human recombinant angiotensin type 1 receptors

Journal of the Renin-angiotensin-aldosterone System : JRAAS
P M VanderheydenGeorges Vauquelin

Abstract

The aim of the present work was to investigate the binding properties of the selective AT(1)-receptor antagonist irbesartan to human AT(1)-receptors by direct radioligand binding. For this purpose the specific binding of [(3)H]-irbesartan to intact Chinese Hamster Ovary (CHO) cells expressing human recombinant AT(1)-receptors was determined. Specific binding of [(3)H]-irbesartan rapidly reached equilibrium and was saturable with a KD of 1.94 +/- 0.12 to a homogeneous class of binding sites. Its binding was inhibited by other AT(1) antagonists (AIIAs) with the same potency order as previous results from [(3)H]-angiotensin II and [(3)H]-candesartan binding to human AT(1)-receptors. Whereas the dissociation rate of [(3)H]-irbesartan was essentially independent of the radioligand concentration, it was much slower at 12 degrees C when compared with 37 degrees C. Moreover, the dissociation rate was similar, as determined in washout experiments in the absence or presence of unlabelled AT(1) antagonists. At 37 degrees C the dissociation rate constant corresponded to a half-life of approximately seven minutes, which is sufficient to explain the partially insurmountable inhibition by irbesartan in previous studies. In contrast, other phe...Continue Reading

References

Jan 1, 1995·Journal of Cardiovascular Pharmacology·S MochizukiA Tomiyama
Oct 15, 1993·European Journal of Pharmacology·C DeliséeP Chatelain
Jan 14, 1997·European Journal of Pharmacology·M OjimaK Nishikawa

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Citations

Sep 18, 2002·Biochemical Pharmacology·Ilse VerheijenGeorges Vauquelin
Apr 8, 2006·Journal of Hypertension. Supplement : Official Journal of the International Society of Hypertension·Georges VauquelinIsabelle Van Liefde
Jul 16, 2008·Molecular and Cellular Endocrinology·I Van Liefde, G Vauquelin
Jan 22, 2005·Fundamental & Clinical Pharmacology·G Vauquelin, I Van Liefde
Jan 26, 2016·British Journal of Pharmacology·Georges VauquelinDavid C Swinney

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