Binding of valsartan to mammalian angiotensin AT1 receptors.

Ciba-Geigy Ltd., Research Department, Pharmaceuticals Division, Basle, Switzerland.

Regulatory peptides 1995 Nov 10

The binding characteristics of the angiotensin AT1 receptor antagonist valsartan were investigated in different animal species and tissues. Using [125I](Sar1,Ile8) angiotensin II as radioligand, affinity constants were determined in liver and adrenal rat and marmoset, human adrenal and in rat aortic smooth muscle cells. In all tissues tested, valsartan had a greater affinity for the AT1 receptor than losartan (on average 5-fold). The affinities of both antagonists were up to 30 times weaker in the dog tissues [3H]Valsartan bound with high affinity (Kd 1.44 nmol/l) to the rat aortic smooth muscle cell AT1 receptor. Binding was saturable and reversible. Non-specific binding was low (10%). Reports that [3H]losartan binds to a non-angiotensin II binding site in rat liver and in other tissues could be confirmed. [3H]Valsartan on the other hand bound only to the AT1 receptor. Using a competition binding assay with [3H]losartan on rat liver membranes it could be shown that valsartan can bind to the 'losartan binding site', but at a 10,000-fold less affinity than for the AT1 receptor. Valsartan is therefore a highly specific and selective antagonist of the AT1 receptor. Due to its high affinity and low non-specific binding it is a suitable radioactive antagonist for the study of the distribution and function of the angiotensin AT1 receptor.