Comparison of affinities of antagonists for wild-type D2 and D4 receptors and mutant D2 receptors
| Mutants | N-Methylspiperone | CPPMA | Clozapine | ||||||
|---|---|---|---|---|---|---|---|---|---|
| KD | KDD2/KDmut | n | KI | KID2/KImut | n | KI | KID2/KImut | n | |
| pM | nM | nM | |||||||
| D4 | 360 ± 70 | 0.2 | 3 | 0.78 ± 0.28 | 1180 | 7 | 12.4 ± 0.6 | 23 | 2 |
| D2 | 79 ± 8 | 1 | 3 | 920 ± 200 | 1 | 6 | 280 ± 30 | 1 | 2 |
| D2W90L | 150 ± 7 | 0.5 | 3 | 330 ± 20 | 2.8 | 3 | 106 ± 2 | 2.5 | 2 |
| D2V91F | 28 ± 17 | 2.8 | 2 | 9.5 ± 4.0 | 97 | 3 | 5.7 ± 0.9 | 49 | 3 |
| D2L94S | 300 ± 10 | 0.3 | 2 | 540 ± 50 | 1.7 | 6 | 780 ± 20 | 0.4 | 2 |
| D2F110L | 230 ± 10 | 0.3 | 3 | 174 ± 46 | 5.3 | 4 | 560 ± 110 | 0.5 | 2 |
| D2V111M | 910 ± 40 | 0.1 | 2 | 1650 ± 80 | 0.6 | 4 | 370 ± 90 | 0.8 | 2 |
| D2F164A/S167A | 112 ± 12 | 0.7 | 2 | 810 ± 110 | 1.1 | 4 | 430 ± 90 | 0.7 | 2 |
| D2L170V/F172C | 110 ± 13 | 0.7 | 2 | 750 ± 200 | 1.2 | 4 | 1650 ± 1250 | 0.2 | 2 |
| D2F189Y | 33 ± 23 | 2.4 | 2 | 340 ± 40 | 2.7 | 4 | 51 ± 1 | 5.5 | 2 |
| D2V196C | 110 ± 10 | 0.7 | 2 | 550 ± 80 | 1.7 | 3 | 370 ± 210 | 0.8 | 2 |
| D2T392V | 110 ± 10 | 0.7 | 2 | 750 ± 60 | 1.2 | 4 | 280 ± 180 | 1 | 2 |
| D2Y408V | 310 ± 7 | 0.3 | 2 | 280 ± 10 | 3.2 | 4 | 60 ± 4 | 4.7 | 2 |
| D2F411V | 102 ± 11 | 0.8 | 2 | 790 ± 230 | 1.2 | 3 | 200 ± 80 | 1.4 | 2 |
K Ds for N-methylspiperone were determined by fitting data to the equation for homologous competitive binding with ligand depletion as described in Experimental Procedures.K I values for CPPMA and clozapine were calculated from IC50 values with the equation of Cheng and Prusoff (1973). Data are means ± S.E. The three mutants in bold had >3-fold increases in affinity for CPPMA.