Fig. 5.

Different muscarinic subtype-selectivity profiles were observed for various PAMs. Increasing concentrations of each PAM, VU0119498 (A), VU0027414 (B), VU0090157 (C), and VU0029767 (D), were added before the application of an appropriate EC₂₀ concentration of ACh determined individually for each muscarinic receptor subtype, and calcium-generated fluorescence changes were measured. Average ACh EC₂₀:M₁ (▪, 1.4 nM), M₂ (□, 13.2 nM), M₃ (•, 0.12 nM), M₄ (○, 23.7 nM), and M₅ (▴, 0.20 nM). The M₂ and M₄ receptors were coexpressed with the chimeric G protein, G_qi5, to permit coupling of these G_i/o-coupled receptors to calcium mobilization. Data represent the mean ± S.E.M. of at least three independent experiments performed in quadruplicate.