TABLE 1.
Effects of Ala and conserved substitutions on [3H]granisetron binding affinities at the 5-HT3 receptor
| Alanine mutant | pKd (nM) Mean ± SE | Kd (nM) | n | Conserved mutant | pKd (nM) Mean ± SE | Kd (nM) | n |
|---|---|---|---|---|---|---|---|
| Wild-type | 9.30 ± 0.12 | 0.5 | 11 | Wild-type | 9.30 ± 0.12 | 0.5 | 11 |
| S177A | 9.23 ± 0.26 | 0.7 | 5 | S177T | 7.86 ± 0.09† | 14* | 3 |
| L178A | 8.02 ± 0.09† | 10 | 4 | L178I | NB† | — | 4 |
| T179A | 8.55 ± 0.09† | 3.2 | 8 | T179S | 9.33 ± 0.22 | 0.5 | 7 |
| F180A | NB† | — | 5 | F180Y | 8.19 ± 0.08† | 6.5 | 3 |
| T181A | 9.38 ± 0.18 | 0.4 | 7 | T181S | 9.15 ± 0.11 | 0.7 | 4 |
| S182A | 9.06 ± 0.10 | 0.9 | 6 | S182T | 8.71 ± 0.03† | 1.9 | 8 |
| W183A | NB† | — | 6 | W183Y | 8.38 ± 0.10† | 4.2 | 6 |
| L184A | 8.42 ± 0.10† | 4.1 | 4 | L184I | 9.12 ± 0.03 | 0.8 | 6 |
| H185A | 8.86 ± 0.11 | 1.4 | 5 | H185N | 8.45 ± 0.07† | 3.5 | 5 |
| T186A | 9.26 ± 0.06 | 0.6 | 9 | T186S | 8.17 ± 0.06† | 6.8 | 4 |
| I187A | 7.90 ± 0.04† | 13* | 4 | I187L | 8.90 ± 0.14 | 1.3 | 8 |
| Q188A | 9.22 ± 0.15 | 0.6 | 7 | Q188N | NB† | — | 4 |
| D189A | NB† | — | 4 | D189E | NB† | — | 7 |
| I190A | NB† | — | 5 | I190L | 8.93 ± 0.02 | 1.2 | 4 |
| N191A | NB† | — | 5 | N191Q | 8.20 ± 0.11† | 6.3 | 4 |
†
Significantly different when compared to wild-type (ANOVA with Dunnett's post test: p < 0.05). NB, No binding or Kd values ≥ 10 nM, which is the resolution of the technique (16); thus values obtained that are >10 nM (*) may be inaccurate.