A Novel Biological Activity of Praziquantel Requiring Voltage-Operated Ca2+ Channel β Subunits: Subversion of Flatworm Regenerative Polarity
Figure 3
PZQ-evoked bipolarity is Ca2+-dependent.
(A) Effect of increasing medium Ca2+ concentration ([Ca2+]out: left, Ca2+ free (1 mM EGTA); right, 1 µM to 10 mM) on bipolarity evoked by PZQ (24 hr exposure). (B) Left & Middle, [K+]out (30 mM) potentiated PZQ-evoked bipolarity (25 µM) over various durations of exposure. Right, nicarpidine (5 µM) antagonized PZQ-evoked bipolarity (50 µM, 24 hrs). Asterisks indicate significance (* = p<5%, ** = p<2%, *** = p<1%) relative to PZQ treatment alone. (C) Screen of Ca2+ signaling modulators and selected other agents (48 hr exposure) in the regenerative assay arrayed in terms of decreasing bipolarity. Bipolarity was not observed with the majority of drugs. Drug source, concentration and assay conditions are detailed in Table S1. Positive control is heptanol (350 µM, [20]).