In the present study,
3
H
-candesartan binding experiments were performed on intact Chinese Hamster Ovary cells transfected with the human AT
1 receptor (CHO-AT
1 cells). Cells were pre-treated with ...0.01
mg/ml saponin or filipin. Both pre-treatments resulted in an increased dissociation rate and decreased affinity of the insurmountable non-peptide antagonist
3
H
-candesartan. A similar decrease in affinity was observed for the peptide antagonist Sar
1-Ile
8 angiotensin II and for other non-peptide antagonists, irrespectively of their degree of insurmountability. A similar discrepancy in
3
H
-candesartan binding was earlier observed when comparing intact CHO-AT
1 cells and membrane preparations thereof. This similarity is further highlighted by the observations that saponin or filipin no longer affect
3
H
-candesartan binding to CHO-AT
1 cell membranes and that both agents permeabilise the CHO-AT
1 cells. This suggests that the intracellular composition and/or organisation of living cells play an active role with regard to antagonist–AT
1 receptor interactions.
