Functional properties of GABA, THIP, and Thio-THIP at human GABAARs expressed in Xenopus oocytesa
| EC50 (pEC50 ± SEM) | nH ± SEM | Rmax ± SEM | n | |
|---|---|---|---|---|
| GABA | ||||
| α1β2γ2S | 38 (4.43 ± 0.09) | 1.1 ± 0.05 | 100 | 5 |
| α1β3γ2S | 42 (4.38 ± 0.11) | 0.9 ± 0.06 | 100 | 4 |
| α2β2γ2S | 46 (4.34 ± 0.08) | 1.2 ± 0.12 | 100 | 4 |
| α2β3γ2S | 16 (4.80 ± 0.14) | 1.1 ± 0.10 | 100 | 5 |
| α5β2γ2S | 42 (4.38 ± 0.05) | 1.1 ± 0.06 | 100 | 5 |
| α5β3γ2S | 14 (4.85 ± 0.08) | 1.1 ± 0.10 | 100 | 4 |
| α4β1δ (monophasic) | 0.62 (6.20 ± 0.65) | 0.4 ± 0.02 | 100 | 4 |
| α4β1δ (triphasic) | EC50, 1∼0.17 (∼6.8) | ND | (7 ± 2)b | |
| EC50, 2∼3.9 (∼5.4) | ND | (65 ± 5)b | ||
| EC50, 3 ND | ND | 100c | 4 | |
| α4β2δ | 2.5 (5.60 ± 0.20) | 1.0 ± 0.09 | 100 | 4 |
| α4β3δ (biphasic) | EC50, 1 0.011 (7.95 ± 0.15) | 0.9 ± 0.17 | (66 ± 7)b | |
| EC50, 2 3.2 (5.50 ± 0.15) | 0.7 ± 0.13 | 100 | 8 | |
| α4β3 | 0.31 (6.51 ± 0.01) | 0.7 ± 0.07 | 100 | 3 |
| α6β2δ | 0.58 (6.24 ± 0.08) | 0.9 ± 0.06 | 100 | 5 |
| α6β3δ | 0.87 (6.06 ± 0.15) | 1.0 ± 0.05 | 100 | 5 |
| ρ1 | 1.8 (5.74 ± 0.05) | 1.7 ± 0.40 | 100 | 4 |
| α4β2NTD/β3TMD/ICLδ | 2.0 (5.70 ± 0.15) | 0.9 ± 0.05 | 100 | 6 |
| α4β3NTD/β2TMD/ICLδ | 1.1 (5.97 ± 0.08) | 0.9 ± 0.08 | 100 | 5 |
| THIP | ||||
| α4β1δ (biphasic) | EC50, 1∼0.14 (∼6.9) | 0.9 ± 0.13 | (105 ± 31)b | |
| EC50, 2 ND | ND | 291 ± 3c | 2 | |
| α4β1δ (triphasic) | EC50, 1∼0.32 (∼6.5) | ND | (41 ± 2)b | |
| EC50, 2∼13 (∼4.9) | ND | (135 ± 6)b | ||
| EC50, 3 ND | ND | 312 ± 26c | 7 | |
| α4β2δ | 33 (4.48 ± 0.04) | 0.7 ± 0.05 | 230 ± 9 | 4 |
| α4β3δ | 130 (3.90 ± 0.24) | 0.7 ± 0.13 | 240 ± 12 | 4 |
| Thio-THIP (agonist) | ||||
| α5β3γ2S | ND | ND | 9 ± 1c | 6 |
| α4β1δ (biphasic) | EC50, 1∼1.0 (∼6.0) | ND | (25 ± 5)b | |
| EC50, 2 ND | ND | 41 ± 1c | 6 | |
| α4β2δ | ND | ND | 4.3 ± 1c | 7 |
| α4β3δ | 13 (4.89 ± 0.13) | 0.61 ± 0.11 | 58 ± 7 | 9/25e |
| α4β3 | ND | ND | 6.5 ± 2c | 4 |
| α6β2δ | ∼220 (∼3.7) | ND | 50 ± 8d | 4 |
| α6β3δ | ∼320 (∼3.5) | ND | 56 ± 11d | 6 |
| ρ1 | ND | ND | 2 ± 3c | 4 |
| α4β2NTD/β3TMD/ICLδ | ND | ND | 14 ± 4c | 7 |
| α4β3NTD/β2TMD/ICLδ | ND | ND | 12 ± 3c | 8 |
| Thio-THIP (antagonist) | ||||
| α1β2γ2S | ∼300 (∼3.5)f | — | — | 3 |
| α1β3γ2S | ∼400 (∼3.4)f | — | — | 8 |
| α2β2γ2S | ∼300 (∼3.5)f | — | — | 4 |
| α2β3γ2S | ∼800 (∼3.1)f | — | — | 3 |
| α5β2γ2S | ∼600 (∼3.2)f | — | — | 6 |
| α4β2δ | >1000 (<3.0)f | — | — | 5 |
| ρ1 | ∼150 (∼3.8)f | — | — | 4 |
↵aEC50 (in μm, with pEC50 values in parentheses), nH, and Rmax (in % of the maximum response of GABA) values are given for the three agonists, and estimated IC50 values (in μm, with pIC50 in parentheses) are given for Thio-THIP at the receptors where it was tested as an antagonist (using GABA EC80 as agonist). The numbers of experiments performed (n) are also given. ND, Not determinable.
↵bFitted maximal response for the phase (in % of Rmax of GABA at the receptor).
↵cThe concentration–response curve was not saturated at the highest agonist concentration tested. Thus, EC50 and nH values could not be determined; and instead of the Rmax value, the response elicited by the maximum agonist concentration used (1 mm THIP or 1 mm Thio-THIP) is given in % of Rmax of GABA at the receptor.
↵dThe concentration–response curve was not completely saturated at the highest agonist concentration tested. EC50 and Rmax are estimated from the fitted curve.
↵eThe averaged EC50 and nH values for Thio-THIP are based on 9 complete concentration–response curves, whereas the averaged Rmax value is based on 25 determinations.
↵fThe concentration-inhibition curve was not completed at the highest Thio-THIP concentration tested. The IC50 value is estimated from the fitted curve.