Antagonistic action of W84 at M1/M4-like receptors in rabbit vas deferens (RDV), at M2 receptors in guinea-pig atria (GPA), and at M3 receptors in guinea-pig ileum (GPI)
| Subtype | Agonist | Cooperativity model | Competitive model | ||
|---|---|---|---|---|---|
| KA | α | KB (Constrained plot) | Slope | ||
| nm | nm | ||||
| M1/M4(RDV) | McN | N.D. | N.D. | 759 ± 67 | 1.15 ± 0.06 |
| M2(GPA) | Oxo | 137 ± 28 | 311 ± 16 | N.D. | N.D. |
| APE | 180 ± 11 | 495 ± 108 | N.D. | N.D. | |
| M3(GPI) | APE | N.D. | N.D. | 4,370 ± 820 | 1.21 ± 0.23 |
The equilibrium dissociation constants K A and cooperativity factors α for the allosteric interaction of W84 with oxotremorine (Oxo) and APE, respectively, at M2 receptors were derived from an analysis based on the cooperativity model. The interaction of W84 with 4-Cl-McN-A-343 (McN) at M1/M4and APE at M3 receptors was analysed according to Arunlakshana and Schild (1959). Because the slopes of the Schild plots did not differ significantly (p > 0.05, ttest) from unity, K B values were estimated by fitting to the data the best straight line with a slope of 1.00. Listed are mean values ± standard error of three to eight experiments performed in separate preparations.
N.D., not determined.