Effects of the PLC inhibitor U73122 on antidepressant-mediated CDP-diacylglycerol production and inositol phosphate accumulation. Cerebrocortical or hippocampal slices labeled with either [3H]inositol or [3H]cytidine were incubated in parallel with buffer alone or the indicated concentrations of U73122, followed by addition of 100 μM fluoxetine (FLU) or 300 μM imipramine (IMI), paroxetine (PAR), maprotiline (MAP), nomifensine (NOM), or SKF38393 (SKF) as indicated. Accumulated [3H]CDP-diacylglycerol (A) or [3H]inositol phosphates (B) were determined after 90 min. While only the hippocampus data are shown for inositol phosphates and the cortical data for CDP-diacylglycerol, each analyte was assessed in each brain region with similar results. Each bar is the mean ± SEM (n = 6). U73122 completely blocked [3H]inositol phosphate accumulation stimulated by either antidepressant agent (ANOVA, p < 0.001). Conversely, U73122 only partially reduced antidepressant drug-induced [3H]CDP-diacylglycerol production. The phospholipase C inhibitor by itself showed slight but significant effects on either analyte. *p < 0.01 compared to effects of antidepressant alone (Dunnett test).
Tyeryar et al. BMC Neuroscience 2008 9:12 doi:10.1186/1471-2202-9-12