TABLE 4

Affinities of drugs in competing for specific 125IBE binding to α 1-AR subtypes expressed alone and together in HEK293 cells

Differentially tagged α 1-AR subtypes were expressed alone or together in HEK293 cells, membranes were harvested, and inhibition of specific 125IBE binding was determined for the drugs indicated. pKi values were calculated by nonlinear regression of one- or two-site fits as described under Materials and Methods. Values are presented as mean ± S.E.M. of three experiments performed in duplicate.

Subtypes Expressed pKi (+)-Niguldipine BMY7378
NE Prazosin pKi high pKi low pKi high pKi low
α1a alone 4.9 ± 0.07 9.3 ± 0.18 10.3 ± 0.09 6.3 ± 0.04
α1b alone 5.2 ± 0.04 9.7 ± 0.07 7.1 ± 0.08 6.6 ± 0.04
α1d alone 6.7 ± 0.06 9.8 ± 0.22 6.9 ± 0.35 8.8 ± 0.16
α1a + α1b 5.2 ± 0.05 9.3 ± 0.04 10.2 ± 0.05 7.3 ± 0.09 N.D. N.D.
α1a + α1d N.D. 9.3 ± 0.10 N.D. N.D. 8.8 ± 0.21 6.4 ± 0.05
α1b + α1d 5.3 ± 0.04 9.6 ± 0.05 N.D. N.D. 8.8 ± 0.24 6.5 ± 0.10
  • N.D., not determined.