TABLE 2

Pharmacological values used for α1-AR subtype–selective antagonist Schild regression analyses

Phenylephrine-stimulated concentration–response curves were calculated for stimulating DMR responses in SW480 cells. Log molar agonist potencies (pEC50) were calculated using the time at which peak DMR response was observed in the absence and presence of various α-AR antagonists (concentration of antagonist used shown in brackets for each phenylephrine pEC50 value). Agonist potencies were subsequently used to calculate antagonist affinity and slope via Schild regression analysis. All data were analyzed with GraphPad Prism and are expressed as mean ± S.E.M. of two to four independent experiments performed with four replicates.

AntagonistPhenylephrine pEC50 ± S.E.M.Schild Analysis
ControlDose 1Dose 2Dose 3Dose 4pA2Slope
Phentolamine−5.12 ± 0.03−4.52 ± 0.03 (300 nM)−4.19 ± 0.04 (1 μM)−3.54 ± 0.06 (3 μM)−3.11 ± 0.1 (10 μM)−6.93 ± 0.511.03 ± 0.08
Doxazosin−5.56 ± 0.05−5.24 ± 0.05 (10 nM)−5.23 ± 0.03 (30 nM)−4.86 ± 0.04 (100 nM)−4.07 ± 0.08 (300 nM)−7.76 ± 0.271.18 ± 0.34
Terazosin−5.28 ± 0.05−4.98 ± 0.11 (100 nM)−4.52 ± 0.08 (300 nM)−4.06 ± 0.14 (1 μM)−7.81 ± 0.250.93 ± 0.29
Prazosin−5.70 ± 0.06−5.29 ± 0.05 (100 nM)−4.69 ± 0.05 (300 nM)−4.38 ± 0.07^^ (1 μM)−7.47 ± 0.321.07 ± 0.21
Tamsulosin−5.43 ± 0.06−4.87 ± 0.07 (300 nM)−4.54 ± 0.07 (1 μM)−4.38 ± 0.1 (3 μM)−4.05 ± 0.1 (10 μM)NDND
5-Methylurapidil−5.45 ± 0.1−5.17 ± 0.14 (300 nM)−4.84 ± 0.14 (1 μM)−4.89 ± 0.25 (3 μM)−4.21 ± 0.23 (10 μM)NDND
Niguldipine−5.65 ± 0.08−5.08 ± 0.11 (3 μM)−3.82 ± 0.15 (10 μM)NDND
Cyclazosin−5.42 ± 0.11−4.86 ± 0.12 (10 nM)−4.62 ± 0.09 (30 nM)−4.01 ± 0.11 (100 nM)−8.37 ± 0.190.97 ± 0.21
BMY7378−5.14 ± 0.03−4.57 ± 0.05(300 nM)−4.13 ± 0.03 (1 μM)−3.57 ± 0.07 (3 μM)−3.21 ± 0.1 (10 μM)−6.87 ± 0.471.06 ± 0.01
  • ND, not determined.

  • ^^ Indicates agonist concentration–response curve Hill slope is <1, as determined by nonlinear regression curve four-parameter variable slope analysis.