Figure 4.

mGlu₅ NAMs exhibit cell type-specific bias. HEK cells expressing mGlu₅, striatal, hippocampal, and cortical cultures were prepared as described in Methods. A range of concentrations of mGlu₅ NAMs (MPEP, Fenobam, RG7090, AZD2066, and AFQ056) were added to the Fura-2 AM loaded cells in 96-well plates and incubated for 20 min. Quis was added at the cell specific EC₈₀ value determined in Figure 3, and Ca²⁺ responses were measured as described in Methods. (A–E) Inhibition curves for each NAM are as indicated. Inhibition curves were generated from the mean data of three independent experiments performed in triplicate. Error bars represent SEM. Data are plotted as a percentage of the EC₈₀ response to Quis. IC₅₀ values of each mGlu₅ NAM in all cell types were determined using Prism curve fitting software from GraphPad (Table 3).