FIGURE 2.

Compound screen identifies modulators of zaprinast-induced Ca²⁺ signaling. A, GCaMP5-expressing parasites pretreated with Cpd2 or a vehicle control were stimulated with zaprinast or a vehicle control, and fluorescence was measured to determine a Z′ score for a zaprinast-based screen for Ca²⁺ modulators. B, GCaMP5-expressing parasites were pretreated with 823 compounds from the PKIS libraries. Fluorescence was measured after zaprinast stimulation. Results are -fold change from zaprinast alone after background subtraction. Compounds that fluoresced independently are indicated (blue) along with selected enhancers (Enh; green) and inhibitors (Inh; red). The mean ± S.D. (error bars) of two experiments is shown, and dashed lines indicate two S.D. values above and below the mean of all compounds. C, structures of Enh1, Enh2, Inh1, and Inh2 as well as the known PKG inhibitors: Cpd1 and Cpd2. D, cumulative frequencies of screen values for all compounds (black), Inh1 and its analogs (red), or Enh1 and its analogs (green).