Table 2.
Affinity of representative nicotinic ligands for purified α6β2*-nAChRs from rat superior colliculus. Comparison with their functional potency at human recombinant α6/3β2βV273S receptors and rodent native α6β2*-nAChRs
| Rat α6β2* | Human α6/3β2β3V273S | Rat or mouse α6β2* | |
|---|---|---|---|
| [125I]-epibatidine binding | Ca2+ entrance (FLIPR) | α-conotoxin MII-sensitive [3H] dopamine release | |
| pKi | pEC50(IA) | pEC50(IA) | |
| Agonists | |||
| A-85380 | 10.7 ± 0.6 | 9.5 ± 0.1 (0.8) | 8.9 (0.8)a |
| Sazetidine A | 10.7 ± 0.3 | 9.3 ± 0.1 (0.6) | ND |
| Varenicline | 8.9 ± 0.7 | 8.0 ± 0.1 (0.3) | 7.1 (0.4)b |
| Cytisine | 8.7 ± 0.4 | 7.7 ± 0.1 (0.6) | 7.5 (0.7)a |
| Nicotine | 8.0 ± 0.5 | 7.4 ± 0.1 (1.0) | 6.1 (1.0)a |
| pKi | pIC50 | pIC50 | |
|---|---|---|---|
| Antagonists | |||
| α-Conotoxin MII | 8.3 ± 0.2c | 8.3 ± 0.05 | 8.6a; 9.0d |
| α-Conotoxin PIA | 7.4 ± 0.4c | 7.6 ± 0.1 | 8.8d |
| MLA | 6.7 ± 0.5c | 7.0 ± 0.1 | 6.4a |
| α-Cntx MII[H9A;L15A] | 5.5 ± 0.6 | 6.8 ± 0.1 | ND |
| DHβE | 6.2 ± 0.6 | 6.7 ± 0.1 | 6.0a |
| Mecamylamine | <5.3 | 5.5 ± 0.1 | Full inhibition at 10 µMe |
| α-Bungarotoxin | <5.3 | <5.0 | No inhibition up to 40 nMe |
EC50, concentration giving 50% of maximal activation; IA, intrinsic activity; IC50, concentration giving 50% of maximal inhibition; ND, not determined.
Data from Salminen et al. (2004); pEC50 and pIC50 converted from EC50 and IC50 respectively; IA derived from the maximum release (Rmax) of compound and the Rmax of nicotine; IC50 were determined at a pulse of 3 µM nicotine (submaximal concentration).
Grady et al. (2010); pEC50 converted from EC50; IA derived from efficacy of compound for activation as % nicotine effect for activation.
Data analysis revealed the existence of a second, low affinity binding site in the µM range (not reported).
Azam and McIntosh (2005); pIC50 converted from IC50; IC50 values were determined at a pulse of 3 µM nicotine (submaximal concentration).
Data from Mogg et al., 2002. Results are the mean ± SEM of at least 3 experiments.