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

Joan Sallés, Maider López de Jesús, Oscar Goñ, Alberto Fernaández-Teruel, Peter Driscol, Adolf Tobeña, Rosa Maria Escorihuela

Research output: Contribution to journalArticleResearchpeer-review

18 Citations (Scopus)

Abstract

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.
Original languageEnglish
Pages (from-to)115-125
JournalPsychopharmacology
Volume154
Issue number2
DOIs
Publication statusPublished - 1 Jan 2001

Keywords

  • Cerebral cortex
  • G-protein
  • Genetic selection
  • Gα q/11
  • Hippocampus
  • Muscarinic receptor
  • Phospholipase C-β isozyme
  • Roman/Verh rat line

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