Chronic Lithium Treatment Impairs Phosphatidylinositol Hydrolysis in Membranes from Rat Brain Regions

Ling Song, Richard S. Jope

Research output: Contribution to journalArticle

57 Scopus citations

Abstract

Membranes prepared from rat brain regions were used to measure the receptor-coupled and/or guanine nucleotide-binding protein (G protein)-mediated hydrolysis of exogenous [3H]phosphatidylinositol ([3H]PI). Guanosine 5′-O-(3-thiotriphosphate) (GTPγS) and NaF (in the presence of AlCl3) caused concentration-dependent stimulations of [3H]PI hydrolysis, supporting the conclusion that G proteins mediating [3H]PI hydrolysis can be activated in this preparation. Neither of these responses was altered by in vitro incubation with 8 mM LiCl, but both were reduced in hippocampal, striatal, and cortical membranes from rats that had been treated with lithium for 4 weeks compared with controls. Two cholinergic agonists, carbachol and pilocarpine, induced no hydrolysis of [3H]PI unless GTPγS was also present, in which case each equally stimulated [3H]PI hydrolysis above that obtained with GTPγS alone. In the presence of GTPγS several excitatory amino acid agonists stimulated [3H]PI hydrolysis to an extent similar to that of carbachol. After chronic lithium treatment, [3H]PI hydrolysis stimulated by carbachol was significantly attenuated, but the response to quisqualate was unaffected. Therefore, lithium added in vitro does not have an effect on cholinergic receptor- or G protein-mediated [3H]PI hydrolysis, but each of these is reduced by chronic lithium treatment. Because exogenous [3H]PI was provided as the substrate, it is evident that the inhibitory effect of chronic lithium treatment cannot be due to substrate depletion. Impaired function of G proteins appears to be the most likely mechanism accounting for attenuated [3H]PI hydrolysis after chronic administration of lithium.

Original languageEnglish (US)
Pages (from-to)2200-2206
Number of pages7
JournalJournal of neurochemistry
Volume58
Issue number6
DOIs
StatePublished - Jun 1992
Externally publishedYes

Keywords

  • Cholinergic system
  • Glutamate
  • Guanine nucleotide-binding proteins
  • Lithium
  • Phosphatidylinositol
  • Phosphoinositides

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

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