TABLE 4

Transduction ratios of AT1 receptor ligands

HEK293 cells expressing the AT1 receptor were stimulated with the different analogs and responses were measured for six distinct signaling pathways. Data were analyzed by nonlinear regression using the operational model equation as described in Materials and Methods to determine log(τ/KA). ΔLog(τ/KA) values were calculated from log(τ/KA) using AngII as the reference ligand. Data are the mean ± S.E.M. of three to six independent experiments performed in triplicate.

GqβArrestin1βArrestin2G12PKC-ERKEGFR-ERK
Log(τ/KA)ΔLog(τ/KA)Log(τ/KA)ΔLog(τ/KA)Log(τ/KA)ΔLog(τ/KA)Log(τ/KA)ΔLog(τ/KA)Log(τ/KA)ΔLog(τ/KA)Log(τ/KA)ΔLog(τ/KA)
AngII8.46 ± 0.070.00 ± 0.108.29 ± 0.120.00 ± 0.168.42 ± 0.060.00 ± 0.088.25 ± 0.070.00 ± 0.108.96 ± 0.040.00 ± 0.068.76 ± 0.040.00 ± 0.06
[Sar1]AngII8.75 ± 0.070.29 ± 0.098.40 ± 0.280.11 ± 0.298.24 ± 0.06−0.18 ± 0.088.48 ± 0.220.23 ± 0.238.72 ± 0.12−0.25 ± 0.128.55 ± 0.15−0.22 ± 0.15
[Ile4]AngII4.50 ± 0.41−3.95 ± 0.415.25 ± 0.07−3.04 ± 0.135.27 ± 0.08−3.15 ± 0.105.02 ± 0.22−3.23 ± 0.226.43 ± 0.24−2.53 ± 0.245.94 ± 0.13−2.82 ± 0.13
[Sar1Ile4]AngII4.98 ± 0.23−3.47 ± 0.235.90 ± 0.17−2.39 ± 0.206.07 ± 0.18−2.35 ± 0.185.76 ± 0.16−2.49 ± 0.187.24 ± 0.36−1.72 ± 0.367.26 ± 0.22−1.51 ± 0.10
[Ile8]AngIINDND6.81 ± 0.36−1.48 ± 0.377.63 ± 0.20−0.79 ± 0.205.15 ± 0.45−3.10 ± 0.454.98 ± 0.20−3.99 ± 0.204.96 ± 0.22−3.81 ± 0.22
[Sar1Ile8]AngIINDND7.50 ± 0.38−0.79 ± 0.397.65 ± 0.22−0.77 ± 0.236.32 ± 0.56−1.93 ± 0.564.84 ± 0.16−4.13 ± 0.164.74 ± 0.04−4.03 ± 0.05
AngIII6.65 ± 0.12−1.80 ± 0.147.29 ± 0.19−0.99 ± 0.227.32 ± 0.16−1.10 ± 0.167.25 ± 0.27−1.00 ± 0.278.26 ± 0.05−0.70 ± 0.068.39 ± 0.15−0.37 ± 0.15
[Ile8]AngIIINDND5.66 ± 0.16−2.63 ± 0.195.55 ± 0.20−2.87 ± 0.214.64 ± 0.15−3.61 ± 0.164.55 ± 0.08−4.42 ± 0.094.95 ± 0.18−3.81 ± 0.18

  • ND, cannot be determined.