Affinities of allosteric ligands for the M1-M4muscarinic receptor subtypes in CHO cell membranes and cooperative interaction between the binding of allosteric ligands and [3H]NMS
| Receptor subtype | Alcuronium | Strychnine | Brucine | Vincamine | Eburnamonine | |
|---|---|---|---|---|---|---|
| M1 | KA | 9.81 ± 0.23 | 10.10 ± 0.40 | 1.78 ± 0.08 | 17.3 ± 0.50 | 7.54 ± 0.09 |
| α | 3.48 ± 0.21 | 0.63 ± 0.05 | 0.68 ± 0.05 | 2.33 ± 0.08 | 2.69 ± 0.02 | |
| M2 | KA | 0.73 ± 0.03 | 11.70 ± 0.70 | 24.30 ± 1.10 | 8.12 ± 0.02 | 68.90 ± 2.40 |
| α | 0.30 ± 0.03 | 0.29 ± 0.03 | 0.52 ± 0.04 | 2.48 ± 0.16 | 0.12 ± 0.02 | |
| M3 | KA | 1.47 ± 0.35 | 2.01 ± 0.09 | 104 ± 5 | 1.85 ± 0.05 | 6.67 ± 1.40 |
| α | 2.64 ± 0.17 | 0.97 ± 0.01 | 1.22 ± 0.07 | 3.09 ± 0.05 | 0.99 ± 0.02 | |
| M4 | KA | 2.49 ± 0.18 | 16.7 ± 0.3 | 0.95 ± 0.05 | 58.90 ± 2.19 | 23.70 ± 2.71 |
| α | 0.74 ± 0.03 | 0.36 ± 0.02 | 0.75 ± 0.04 | 0.14 ± 0.00 | 0.27 ± 0.01 |
Affinities are expressed as Kd values for the binding of allosteric ligands to the receptors (KA ; μm), and magnitudes of the allosteric interactions are described by the cooperativity coefficients α. Data have been computed from measurements of the binding of [3H]NMS in the presence of increasing concentrations of the allosteric ligands and are mean ± standard error of four or five experiments with triplicate incubations.