1 CHO-K1 cells that were stably transfected with the gene for the human AT 1 receptor (CHO-AT 1 cells) were used for pharmacological studies of non-peptide AT 1 receptor antagonists. 2 In the presence of 10 mM LiCl, angiotensin II caused a concentration-dependent and long-lasting increase of inositol phosphates accumulation with an EC 50 of 3.4 nM. No angiotensin II responses are seen in wild-type CHO-K1 cells. 5 Preincubation with the insurmountable antagonist candesartan decreased the maximal angiotensin II induced inositol phosphate accumulation up to 94% and, concomitantly, decreased the maximal binding capacity of the cell surface receptors. These inhibitory e ects were halfmaximal for 0.6 nM candesartan and were attenuated by simultaneous preincubation with 1 mM losartan indicating a syntopic action of both antagonists. 6 Losartan caused a parallel rightward shift of the angiotensin II concentration-response curves and did not a ect the maximal binding capacity. EXP3174 (the active metabolite of losartan) and irbesartan showed a mixed-type behavior in both functional and binding studies. 7 Reversal of the inhibitory e ect was slower for candesartan as compared with EXP3174 and irbesartan and it was almost instantaneous for losartan, suggesting that the insurmountable nature of selective AT 1 receptor antagonists in functional studies was related to their long-lasting inhibition.

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