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

Rationale: One of the major pathways for neurotransmitter signaling involves phosphoinositide-specific and G-protein-dependent phospholipase C-beta (PLC-beta), which stimulates the formation of inositol 1,4,5-trisphosphate and diacylglycerol. Serotonergic and muscarinic-cholinergic signals in the brain are largely mediated through the hydrolysis of phosphoinositides by PLC.
Objectives: The aim of the experiments reported here was to explore the potential differences in neurotransmitter receptor coupling to PLC in Roman high-avoidance (RHA)/Verh and Roman low-avoidance (RLA)/Verh rats, by examining the changes in agonist (carbachol, 5-methyltryptamine)-stimulated phosphoinositide hydrolysis in hippocampal and cortical membranes derived from the two rat lines.
Methods: To investigate changes in receptor and G-protein coupling to PLC in the brains of these two psychogenetically selected rat lines, which differ in their emotional profiles/learning abilities, we examined GTPgammaS-, agonist (carbachol, 5-methyltryptamine)-, and calcium-stimulated 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 of RHA/Ver rats, as compared to their RLA/Verh counterparts. Conversely, GTPgammaS- and agonist-induced PLC activity was less pronounced in the hippocampus of RHA/Verh with respect to RLA/Verh rats. Western blot analysis showed no significant differences in the relative values of the G-proteins alphaq/11 and betagamma subunits between both groups of rats in any brain region. However, the levels of PLC-beta1, PLC-beta3, and PLC-beta4 were significantly lower in the hippocampus of RHA/Verh than in RLA/Verh rats.
Conclusions: It is concluded that the hippocampus of RHA/Verh rats has severe deficiencies in PLC activity stimulated by guanine nucleotides and agonists, which are specifically related to a lower level of expression of the PLC-beta type isozymes, a fact that may account for the differential behavioral phenotype observed in these psychogenetically selected rat lines.