Pharmacological profile of immunoimmobilized nAChRs
| Main subtypes | α6 (α6+/+) α6β2, α4α6β2 | β2 (α6−/−) α4β2 | α6 (α4−/−) α6β2 |
|---|---|---|---|
| Ligand | |||
| Kd, pM | |||
| [125I]Epibatidine | 46 (20) | 75 (34) | 34 (24) |
| Ki, nM | |||
| Cytisine | 0.8 (19) | 0.2 (14) | 1.3 (21) |
| Nicotine | 2.8 (40) | 1.7 (19) | 3.8 (31) |
| ACh | 16.6 (23) | 9.6 (23) | ND |
| Dihydro-β-erythroidine | 611 (21) | 341 (20) | ND |
| d-Tubocurarine | 5072 (20) | 20980 (31) | ND |
| αCtxMII (high affinity) | 2.14 (41) | 1.07 (34) | |
| αCtxMII (low affinity) | >10000 | >10000 | |
| MLA (high affinity) | 123 (87) | 231 (23) | |
| MLA (low affinity) | 21900 (43) | 14300 (27) |
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The Kd and Ki values were derived from saturation and competition binding curves obtained on α6-immunoimmobilized striatal nAChRs from α6+/+ and α4−/− animals [columns α6(α6+/+) and α6(α4−/−), respectively] and on the β2-immunoimmobilized nAChRs from α6−/− animals [β2(α6−/−)]. According to our IPP experiments, the main immunoimmobilized subtypes are indicated. Curves obtained from three to six separate experiments were fitted using a nonlinear least-squares analysis program and the F test. For αCtxMII and MLA, data analysis revealed the existence of a low-and high-affinity binding site in α6* nAChRs of Wt animals. Numbers in parentheses represent the coefficient of variation as a percentage.
