Transmembrane signaling through phospholipase C in cortical and hippocampal membranes of psychogenetically selected rat lines

Rationale: One of the major pathways for neurotransmitter signaling involve s phosphoinositide-specific and G-protein-dependent phospholipase C-beta (P LC-beta), which stimulates the formation of inositol 1,4,5-trisphosphate an d diacylglycerol. Serotonergic and muscarinic-cholinergic signals in the br ain are largely mediated through the hydrolysis of phosphoinositides by PLC . Objectives: The aim of the experiments reported here was to explore the p otential differences in neurotransmitter receptor coupling to PLC in Roman high-avoidance (RHA)/Verh and Roman low-avoidance (RLA)/Verh rats, by exami ning the changes in agonist (carbachol, 5-methyltryptamine)-stimulated phos phoinositide hydrolysis in hippocampal and cortical membranes derived from the two rat lines. Methods: To investigate changes in receptor and G-protei n coupling to PLC in the brains of these two psychogenetically selected rat lines, which differ in their emotional profiles/learning abilities, we exa mined GTP gammaS-, agonist (carbachol, 5-methyltryptamine)-, and calcium-st imulated phosphoinositide hydrolysis in cortical and hippocampal membranes of RHA/Verh and RLA/Verh rats. Results: The results indicated that calcium- induced increase in PLC activity was larger in the cortex and hippocampus o f RHA/Ver rats, as compared to their RLA/Verh counterparts. Conversely, GTP gammaS- and agonist-induced PLC activity was less pronounced in the hippoc ampus of RHA/Verh with respect to RLA/Verh rats. Western blot analysis show ed no significant differences in the relative values of the G-proteins alph a (q/11) and beta gamma subunits between both groups of rats in any brain r egion. However, the levels of PLC-beta (1), PLC-beta (3), and PLC-beta (4) were significantly lower in the hippocampus of RHA/Verh than in RLA/Verh ra ts. Conclusions: It is concluded that the hippocampus of RHA/Verh rats has severe deficiencies in PLC activity stimulated by guanine nucleotides and a gonists, which are specifically related to a lower level of expression of t he PLC-beta type isozymes, a fact that may account for the differential beh avioral phenotype observed in these psychogenetically selected rat lines.