TABLE 2

Potencies, relative efficacies (Emax) and kinetics of activation of cAMP, ERK1/2, calcium signaling pathways, and receptor endocytosis by adrenergic ligands

HEK-HA-β2AR cells were stimulated with different concentrations of clinically relevant adrenergic ligands and responses were measured for 4 distinct signaling pathways (cAMP, 30 minutes; ERK1/2, 2 or 4 minutes; calcium 0–60 seconds and endocytosis 30 minutes). The negative pEC50 values reported for some ligands mean that the curve was biphasic, and these are the pEC50 values for the part of the curve following the Emax. Data are the mean ± S.E.M. of 4–6 independent experiments with repeats in duplicate.

LigandcAMPpERK1/2Ca2+Endocytosis
pEC50Emaxt1/2pEC50EmaxPeakpEC50EmaxPeakpEC50Emaxt1/2
%ISOminutes%ISOminutes%ISOseconds%ISOminutes
ISOa8.23 ± 0.151002.54 ± 0.187.95 ± 0.1310047.47 ± 0.2110018.0 ± 1.087.88 ± 0.261007.64 ± 0.04
EPI7.78 ± 0.2374.04 ± 6.191.64 ± 0.056.79 ± 0.19157.7 ± 14.1326.82 ± 0.08112.0 ± 4.1017.4 ± 0.877.26 ± 0.16115.5 ± 6.2412.26 ± 0.02
NE7.08 ± 0.2588.32 ± 8.531.74 ± 0.166.48 ± 0.12154.6 ± 9.2626.21 ± 0.2458.01 ± 9.4321.7 ± 1.325.64 ± 0.3090.00 ± 12.512.40 ± 0.04
SALBa9.08 ± 0.31111.3 ± 10.52.29 ± 0.1210.81 ± 0.2887.16 ± 5.8927.72 ± 0.2850.93 ± 4.5019.8 ± 0.465.93 ± 0.3144.94 ± 6.865.62 ± 0.34
SALMa8.63 ± 0.20105.5 ± 6.111.94 ± 0.1410.14 ± 0.2374.39 ± 5.2825.80 ± 0.3934.45 ± 6.1030.9 ± 2.86>4.00NRNR
LABa7.82 ± 0.2351.84 ± 3.732.61 ± 0.3810.28 ± 0.28111.9 ± 7.524>4.00NRNR>4.00NRNR
BUCa8.64 ± 0.3862.07 ± 7.482.45 ± 0.168.51 ± 0.41107.2 ± 22.12>4.00NRNR>4.00NRNR
−4.86 ± 0.26
ALP9.81 ± 0.3935.76 ± 3.702.64 ± 0.619.54 ± 0.28102.3 ± 5.714>4.00NRNR>4.00NRNR
−6.63 ± 0.34
PINa9.50 ± 0.4918.43 ± 2.510.96 ± 0.148.90 ± 0.4881.55 ± 19.864>4.00NRNR>4.00NRNR
−5.76 ± 0.34
XAMa>4.00NRNR6.58 ± 0.22102.7 ± 8.634>4.00NRNR>4.00NRNR
PRO>4.00NRNR7.87 ± 0.1377.28 ± 7.184>4.00NRNR>4.00NRNR
−5.79 ± 0.44
CARVa>4.00NRNR7.98 ± 0.1288.55 ± 12.474>4.00NRNR>4.00NRNR
−5.68 ± 0.35
ICI7.95 ± 0.45−35.46 ± 5.3914.15 ± 0.13>4.00NRNR>4.00NRNR>4.00NRNR
BIS6.96 ± 0.77−18.25 ± 5.046.50 ± 1.01>4.00NRNR>4.00NRNR>4.00NRNR
BETa6.75 ± 0.42−39.80 ± 10.85.42 ± 2.69>4.00NRNR>4.00NRNR>4.00NRNR
MET6.87 ± 0.55−39.00 ± 9.466.68 ± 2.46>4.00NRNR>4.00NRNR>4.00NRNR
NEB7.46 ± 0.57−13.79 ± 4.0417.48 ± 3.94>4.00NRNR>4.00NRNR>4.00NRNR
NADa8.24 ± 0.37−34.07 ± 7.803.48 ± 1.57>4.00NRNR>4.00NRNR>4.00NRNR
ATEN5.44 ± 0.44−49.38 ± 10.97.77 ± 1.99>4.00NRNR>4.00NRNR>4.00NRNR
TIM8.81 ± 0.40−44.45 ± 5.284.47 ± 0.11>4.00NRNR>4.00NRNR>4.00NRNR
  • ICI, ICI 118,551; MET, metoprolol; NEB, nebivolol; NR, no response.

  • a Compounds that were selectively signaling via the β2AR.