Equilibrium binding parameters of indolocarbazoles with [3]HNMS and ACh at muscarinic receptors
| Name | M1 | M2 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Cooperativity | Cooperativity | ||||||||
| pK | Slope | [3H]NMS | ACh | pK | Slope | [3H]NMS | ACh | ||
| Staurosporine | Mean | 5.91 | 1.01 | 1.53 | 0.19 | 5.13 | 1.00 | 1.49 | 0.42 |
| SEM | 0.03 | 0.01 | 0.06 | 0.04 | 0.05 | 0.00 | 0.06 | 0.04 | |
| Go 7874 | Mean | 5.77* | 1.60 | 0.54 | 0.07 | 5.03* | 1.91 | 0.66 | 0.24 |
| SEM | 0.16 | 0.17 | 0.04 | 0.00 | 0.16 | 0.08 | 0.00 | 0.11 | |
| KT 5823 | Mean | 5.70 | 1.44 | 8.11 | 1.31 | 5.67* | 1.00 | 3.27 | 1.34 |
| SEM | 0.05 | 0.14 | 1.61 | 0.44 | 0.15 | 0.00 | 0.19 | 0.03 | |
| KT 5720 | Mean | 6.421-a | 1.00 | 1.94 | 1.39 | —1-b | —1-b | —1-b | |
| SEM | 0.09 | 0.00 | 0.14 | 0.09 | |||||
| K-252a | Mean | 5.13* 1-a | 1.00 | 2.62 | 0.86 | ||||
| SEM | 0.14 | 0.00 | 0.68 | 0.13 | |||||
| Name | M3 | M4 | |||||||
|---|---|---|---|---|---|---|---|---|---|
| Cooperativity | Cooperativity | ||||||||
| pK | Slope | [3H]NMS | ACh | pK | Slope | [3H]NMS | ACh | ||
| Staurosporine | Mean | 5.31 | 1.00 | 0.88 | 0.15 | ||||
| SEM | 0.09 | 0.00 | 0.02 | 0.03 | |||||
| Go 7874 | Mean | 5.12* | 1.50 | 0.32 | 0.72 | 5.71* | 1.47 | 0.80 | 0.10 |
| SEM | 0.01 | 0.50 | 0.09 | 0.05 | 0.13 | 0.21 | 0.05 | 0.00 | |
| KT 5823 | Mean | ||||||||
| SEM | |||||||||
| KT 5720 | Mean | 6.42* | 1.00 | 0.92 | 0.55 | ||||
| SEM | 0.25 | 0.00 | 0.01 | 0.08 | |||||
| K-252a | Mean | ||||||||
| SEM | |||||||||
Assays such as those shown in Figs. 2 and 5 were fitted to eq. 1 or 2 as appropriate (see Experimental Procedures).
The results are from at least three assays, except for *n = 2. Empty cells indicate that it was not possible to obtain at least two sets of parameter estimates.
↵1-a Some, but not all, of the values were obtained from analyses in which the affinity for the [3H]NMS-occupied receptor was fixed at the mean value obtained from off-rate assays and shown in Table 2.
↵1-b Inconsistent effects observed (see text).