Fig. 2.

Novel M₁ PAMs potentiated agonist responses in M₁ CHO cells. A, fluorescence ratio trace generated by a potentiator identified via high-throughput screening, VU0090157, in the Ca²⁺ assay. Each point of the raw trace was divided by the fluorescence at time 0 to generate a ratio. Compound was added at 4 s, followed by an EC₂₀ concentration of acetylcholine at 196 s. Traces reflect the increase in fluorescence obtained in the presence of increasing concentrations of compound. B, maximum fluorescence ratio values in the EC₂₀ window (196-225 s) were plotted as a function of compound concentration to generate a concentration-response curve. Potencies of compounds were as follows (mean ± S.E.M.): VU0119498, 3.1 ± 0.2 μM; VU0027414, 2.1 ± 0.5 μM; VU0090157, 5.3 ± 0.7 μM; and VU0029767, 9.4 ± 4.4 μM. Data represent the mean ± S.E.M. of three independent experiments performed in quadruplicate.