TABLE 1.
RegIIA inhibition of α3-containing nAChR subtypes and subtype mutants
IC50 values (nm) with 95% CI. Hill slope (nH) was obtained from concentration–response curves for RegIIA at wild-type and mutant human α3β2 and α3β4 nAChR subtypes. Human α3β2 nAChR mutations hα3β2[T59K] and hα3β2[S113R] notably decrease the IC50 of RegIIA towards the human α3β4 subtype value, whereas the opposite human α3β4[K59T] and α3β4[R113S] result in lower potency of RegIIA and significantly increased IC50 values. Data from wild-type nAChRs and the mutants mentioned are highlighted in bold font. All data represent mean of n = 3–9 experiments.
| nAChR/mutant | IC50 | 95% CI | nH |
|---|---|---|---|
| nm | |||
| hα3β2 | 132.4 | 109.7–159.7 | 1.5 |
| hα3β4 | 45.6 | 31.5–65.9 | 0.9 |
| hα3β2[1–63β4] | 159.2 | 113.0–224.4 | 1.4 |
| hα3β2[70–86β4] | 1268.1 | 935.7–1718.5 | 0.9 |
| hα3β2[T59K] | 49.4 | 33.4–73.1 | 1.2 |
| hα3β4[K59T] | 2795.1 | 2346.6–3329.3 | 1.4 |
| hα3β4[113–115β2] | 1056.5 | 924.9–1206.9 | 1.1 |
| hα3β2[S113R] | 23.7 | 19.0–29.4 | 1.5 |
| hα3β4[R113S] | 805.3 | 554.7–1169.0 | 0.9 |
| hα3β4[S114Y] | 133.1 | 105.0–168.6 | 1.2 |
| hα3β4[N115D] | 275.0 | 221.3–341.5 | 1.6 |
| hα3β4[M163K+T164S] | 138.6 | 113.2–169.8 | 2.3 |
| hα3β4[P165E] | 217.9 | 172.9–274.6 | 1.2 |
| hα3β4[T166V+M169L] | 130.2 | 100.1–169.5 | 1.9 |