Figure 3.

Interactions of the carboxyl group of candesartan with Gln 257 and Thr 287 in the AT₁ receptor. (A) HEK293 cells expressing wild-type AT₁, Gln257Ala or Thr287Ala mutant receptors were pretreated with 1 × 10⁻⁷ M of candesartan (Can) and stimulated by AngII at the indicated concentrations. The activation of ERKs was determined. ^*P<0.05 versus wild-type AT₁. (B) Alteration of cysteine accessibility by mechanical stretch in COS7 cells expressing wild-type AT₁, Gln257Ala or Thr287Ala receptors. The cells were pretreated with or without 1 × 10⁻⁷ M Can and stretched for 0 or 8 min. ^*P<0.05 versus stretch (−), ^#P<0.05 versus stretch (+) in each receptor. (C) HEK293 cells expressing Gln257Ala (left) or Thr287Ala (right) mutant receptor were pretreated with the indicated concentrations of Can and stimulated by mechanical stretch. The activation of ERKs was determined. AngII, angiotensin II; AT₁, AngII type 1; ERK, extracellular signal-regulated protein kinase; HEK, human embryonic kidney cells.