Inhibition of [3H]P1075 binding by KATP channel modulators
| KATPChannel Modulator | SUR2A | SUR2B | Rat Cardiac Membranes | Rat Aortic Strips |
|---|---|---|---|---|
| pKi | pKi | pKi | pKi | |
| P1075 | 7.78 ± 0.02 | 8.48 ± 0.07 | 8.14 ± 0.04 | 8.54 ± 0.03 |
| (−)Pinacidil | 7.11 ± 0.04 | 7.66 ± 0.02 | 7.03 ± 0.05 | 7.66 ± 0.06 |
| Minoxidil sulfate | 6.85 ± 0.05 | 7.28 ± 0.02 | 7.19 ± 0.08 | 7.45 ± 0.10 |
| Levcromakalim | 6.37 ± 0.04 | 6.95 ± 0.03 | 6.62 ± 0.03 | 7.33 ± 0.06 |
| Aprikalim | 5.92 ± 0.01 | 6.49 ± 0.08 | 5.92 ± 0.05 | 7.05 ± 0.05 |
| Diazoxide | 4.47 ± 0.07 | 5.11 ± 0.06 | 4.72 ± 0.05 | 4.66 ± 0.03 |
| Nicorandil | 4.73 ± 0.04 | 5.08 ± 0.06 | 5.03 ± 0.04 | 5.31 ± 0.06 |
| Glibenclamide | 6.50 ± 0.04 | 5.62 ± 0.05 | 7.12 ± 0.09 | 6.36 ± 0.04 |
| AZ-DF 265 | 5.51 ± 0.04 | 5.20 ± 0.05 | 5.95 ± 0.11 | 5.95 ± 0.03 |
Binding experiments with SUR2A were performed as shown in Fig. 7. Logistic equation (see Experimental Procedures) was fitted to individual competition curves (n = 4) yielding pIC50, amplitudes (≈100% with exception of minoxidil sulphate, see below) and Hill coefficients nH (≈1). pIC50 values were corrected for presence of the radiolabel according to equation of Cheng-Prusoff which, on logarithmic scale, corresponded to addition of 0.07. Data for SUR2B are from Hambrock et al. (1998) with exception of values for nicorandil and (−) pinacidil, which were determined in this study. pKi values in rat heart microsomes are from Löffler-Walz and Quast (1998) with a Cheng-Prusoff correction of 0.06, and, those for rat aortic strips from Quast et al., 1993. Temperature was 37°C in all cases. In all four preparations, minoxidil sulfate inhibited [3H]P1075 binding only by 68 to 75%.