Table 2

The Ki values, pEC50 values, R.I.A., and R.e. of selected agonists on α2A-ARs for the Gs and Gi pathways

DrugpKipEC50R.I.A.R.e.
Gs Pathway α2A-H (+PTX)Gi Pathway α2A-L (−PTX)Gs Pathway α2A-H (+PTX)Gi Pathway α2A-L (−PTX)GsPathway α2A-H (+PTX)Gi Pathway α2A-L (−PTX)
l-Epinephrine6.196.757.491.322-a  ± 0.100.752-a  ± 0.050.98  ± 0.030.99  ± 0.02
l-Norepinephrine5.256.006.641.172-a  ± 0.090.842-a  ± 0.070.97  ± 0.090.89  ± 0.07
l-Isoproterenol2.913.795.131.10  ± 0.040.24  ± 0.031.132-b  ± 0.120.132-b  ± 0.02
UK-14,3046.327.357.361.00  ± 0.071.00  ± 0.011.00  ± 0.041.00  ± 0.02
p-Aminoclonidine6.540.57  ± 0.060.55  ± 0.020.32  ± 0.030.29  ± 0.01
BHT-9206.005.986.990.47  ± 0.030.36  ± 0.030.26  ± 0.020.19  ± 0.02
BHT-9334.580.45  ± 0.070.44  ± 0.050.25  ± 0.040.23  ± 0.02
Clonidine7.070.28  ± 0.040.30  ± 0.030.16  ± 0.020.16  ± 0.02
p-Iodoclonidine7.290.28  ± 0.040.302-a  ± 0.030.16  ± 0.02
Xylazine5.500.23  ± 0.030.36  ± 0.030.14  ± 0.020.19  ± 0.01
Guanabenz7.240.21  ± 0.020.18  ± 0.020.12  ± 0.010.09  ± 0.01
Oxymetazoline7.457.637.880.172-a  ± 0.030.482-a  ± 0.04

The Ki values were determined from competition binding against 5 nM [3H]yohimbine in α2A-H whole cells, and the pEC50 and R.I.A. values were determined from functional studies measuring [3H]cAMP accumulation. R.I.A.s were obtained at 20× Ki concentrations of the agonists and are expressed relative to the maximal response of the full agonist UK-14,304, which showed no response in control Neo cells (±PTX). R.e.s were estimated as described in the text (Data Analysis). Values are mean ± S.E.

  • 2-a  Significant response also observed in control Neo cells without the α2A-AR (see Table3), suggesting the involvement of a non-α2A-AR. The reported value therefore simply represents maximal response relative to UK-14,304 rather than a true α2A-AR-mediated R.I.A.

  • 2-b  Difference between R.e.for Gi and Gs response is significant (P = .0012 after Bonferroni's correction for multiple comparison). No other differences are significant after correction for multiple comparisons.