Interaction of the indicated allosteric agents with wild type M5 receptors and related mutants
Minus log values of the factors of cooperativity (pα) are indicated in parentheses on the right of the table. Indicated are mean values ± S.E. of three to ten separate experiments with duplicated values.
| pEC0.5,diss | pKA (pα) | |||||||
|---|---|---|---|---|---|---|---|---|
| M5 | M5477W→A | M5482W→A | M5477W→A + 482W→A | M5 | M5477W→A | M5482W→A | M5477W→A + 482W→A | |
| W84 | 5.41 ± 0.04 | 3.24 ± 0.54 | 5.51 ± 0.04 | 2.75 ± 0.86 | 5.47 ± 0.05a (-0.05 ± 0.05) | 4.72 ± 0.09 (-1.56 ± 0.15) | 5.49 ± 0.03a (0.02 ± 0.04) | 4.50 ± 0.07 (-1.23 ± 0.21) |
| Dimethyl-W84 | 5.40 ± 0.04 | 4.08 ± 0.29 | 5.52 ± 0.07 | 4.41 ± 0.24 | N.D. | N.D. | N.D. | N.D. |
| Naphmethonium | 6.22 ± 0.03 | 4.94 ± 0.17 | 6.20 ± 0.04 | 4.19 ± 0.29 | N.D. | N.D. | N.D. | N.D. |
| Gallamine | 5.41 ± 0.11 | —b | 3.49 ± 0.05 | — | 6.12 ± 0.03 (-1.45 ± 0.11) | 5.05 ± 0.03 (-1.19 ± 0.03) | 5.91 ± 0.15 (-1.35 ± 0.16) | 4.90 ± 0.14 (-1.08 ± 0.10) |
| Diallylcaracurine V | 5.57 ± 0.09 | 5.61 ± 0.05 | 5.43 ± 0.09 | 5.87 ± 0.08 | 6.18 ± 0.06 (-0.82 ± 0.08) | 6.41 ± 0.11 (-0.46 ± 0.02) | 6.13 ± 0.04 (-1.05 ± 0.01) | 6.26 ± 0.15 (-0.40 ± 0.03) |
pEC0.5,diss, minus log concentration reducing [3H]NMS dissociation to half of the control rate; pKA, minus log value of the equilibrium dissociation constant for allosteric agent binding to free receptors; N.D., not determined.
↵ a EC0.5,diss was used for curve fitting because of nearly neutral cooperativity as described under Materials and Methods.
↵ b —, no effect up to minus log concentration = 2.5.