Bell-shaped isotherms for h5-HT1A receptor-mediated stimulation of [35S]GTPγ S binding to Gαi3 subunits
| ← Gαi3 Activation → | Affinity | |||||
|---|---|---|---|---|---|---|
| Ligand | c1 | d | c2 | a2 | n | (pKi) |
| % | % | |||||
| 5-HT | 9.22 ± 0.04 | 245 ± 15 | 7.31 ± 0.06 | 59 ± 9 | 8 | 9.21 |
| S14671 | 9.65 ± 0.10 | 258 ± 19 | 8.50 ± 0.10 | 70 ± 14 | 3 | 10.52 |
| Clozapine | 6.74 ± 0.08 | 267 ± 44 | 4.08 ± 0.12 | 71 ± 26 | 3 | 6.88 |
| S14506 | 9.17 ± 0.07 | 229 ± 17 | 8.19 ± 0.12 | 82 ± 6 | 6 | 9.66 |
| (+)-8-OH-DPAT | 9.26 ± 0.04 | 280 ± 12 | 7.53 ± 0.07 | 82 ± 13 | 7 | 9.33 |
| 5-CT | 9.86 ± 0.06 | 233 ± 14 | 8.27 ± 0.05 | 92 ± 2 | 3 | 10.10 |
| Flesinoxan | 9.16 ± 0.04 | 242 ± 6 | 7.46 ± 0.05 | 120 ± 4 | 3 | 9.26 |
| Ziprasidone | 8.49 ± 0.14 | 255 ± 6 | 6.37 ± 0.16 | 127 ± 19 | 3 | 8.91 |
| (+)-7-OH-DPAT | 7.02 ± 0.06 | 267 ± 19 | 5.17 ± 0.09 | 129 ± 16 | 3 | 7.29 |
| Eltoprazine | 8.14 ± 0.01 | 232 ± 9 | 6.34 ± 0.02 | 143 ± 5 | 3 | 8.19 |
| Buspirone | 8.23 ± 0.07 | 234 ± 2 | 6.45 ± 0.03 | 153 ± 3 | 3 | 8.05 |
| S16924 | 8.67 ± 0.06 | 236 ± 13 | 6.94 ± 0.05 | 166 ± 16 | 3 | 8.74 |
| (−)-8-OH-DPAT | 9.09 ± 0.08 | 284 ± 20 | 7.27 ± 0.16 | 220 ± 20 | 3 | 9.19 |
Activation of Gαi3 G-protein subunits in CHO-h5-HT1A cell membranes was determined employing an antibody-capture/SPA detection technique. 5-HT and other high-efficacy agonists yielded bell-shaped isotherms. Parameters analyzed are as shown in Fig. 4. Data are expressed as mean ± s.e.m. of n independent determinations performed in duplicate. Ligands are listed according to their capacity to induce bell-shaped isotherms. For comparison, ligand affinity (pKi) is shown, as determined by competition binding with [3H]8-OH-8DPAT (Newman-Tancredi et al., 2001a,b)
a2, maximal inhibition of [35S]GTPγ S binding; c1, drug concentration inducing half-maximal stimulation; c2, drug concentration inducing half of the inhibitory effect; d, maximal observed stimulation relative to basal values (=100%).