TY - JOUR
T1 - Transmembrane signaling through phospholipase C in cortical and hippocampal membranes of psychogenetically selected rat lines
AU - Sallés, Joan
AU - López de Jesús, Maider
AU - Goñ, Oscar
AU - Fernaández-Teruel, Alberto
AU - Driscol, Peter
AU - Tobeña, Adolf
AU - Escorihuela, Rosa Maria
PY - 2001/1/1
Y1 - 2001/1/1
N2 - Rationale: One of the major pathways for neurotransmitter signaling involves phosphoinositide-specific and G-protein-dependent phospholipase C-β (PLC-β), 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 GTPγS-, 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/Verh rats, as compared to their RLA/Verh counterparts. Conversely, GTPγS- 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 αq/11 and βγ subunits between both groups of rats in any brain region. However, the levels of PLC-β1, PLC-β3, and PLC-β4 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-β type isozymes, a fact that may account for the differential behavioral phenotype observed in these psychogenetically selected rat lines.
AB - Rationale: One of the major pathways for neurotransmitter signaling involves phosphoinositide-specific and G-protein-dependent phospholipase C-β (PLC-β), 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 GTPγS-, 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/Verh rats, as compared to their RLA/Verh counterparts. Conversely, GTPγS- 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 αq/11 and βγ subunits between both groups of rats in any brain region. However, the levels of PLC-β1, PLC-β3, and PLC-β4 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-β type isozymes, a fact that may account for the differential behavioral phenotype observed in these psychogenetically selected rat lines.
KW - Cerebral cortex
KW - G-protein
KW - Genetic selection
KW - Gα q/11
KW - Hippocampus
KW - Muscarinic receptor
KW - Phospholipase C-β isozyme
KW - Roman/Verh rat line
U2 - 10.1007/s002130000621
DO - 10.1007/s002130000621
M3 - Article
VL - 154
SP - 115
EP - 125
JO - Psychopharmacology
JF - Psychopharmacology
SN - 0033-3158
IS - 2
ER -