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Subacute and Chronic In Vivo Lithium Treatment Inhibits Agonist‐ and Sodium Fluoride‐Stimulated Inositol Phosphate Production in Rat Cortex
Author(s) -
Godfrey Philip P.,
McClue Steven J.,
White Alison M.,
Wood Andrew J.,
GrahameSmith David G.
Publication year - 1989
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1989.tb09148.x
Subject(s) - inositol , carbachol , endocrinology , medicine , inositol phosphate , chemistry , lithium (medication) , agonist , in vivo , phosphatidylinositol , stimulation , muscarinic agonist , phospholipase c , phospholipid , receptor , biochemistry , biology , signal transduction , membrane , microbiology and biotechnology
We have investigated the effects of in vivo lithium treatment on cerebral inositol phospholipid metabolism. Twice‐daily treatment of rats with LiCl (3 mEq/kg) for 3 or 16 days resulted in a 25–40% reduction in agonist‐stimulated inositol phosphate production, compared with NaCl‐treated controls, in cortical slices prelabelled with [ 3 H]inositol. A small effect was also seen with 5‐hydroxytryptamine (5‐HT) 24 h after a single dose of LiCl (10 mEq/kg). Dose–response curves to carbachol and 5‐HT showed that lithium treatment reduced the maximal agonist response without altering the EC 50 value. This inhibition was not affected by the concentration of LiCl in the assay buffer. Stimulation of inositol phosphate formation by 10 m M NaF in membranes prepared from cortex of 3‐day lithium‐treated rats was also inhibited, by 35% compared with NaCl‐treated controls. Lithium treatment did not alter the kinetic profile of inositol polyphosphate formation in cortical slices stimulated with carbachol. Muscarinic cholinergic and 5‐HT 2 bindings were unaltered by lithium, as was cortical phospholipase C activity and isoproterenol‐stimulated cyclic AMP formation. [ 3 H]Inositol labelling of phosphatidylinositol 4,5‐bisphosphate was significantly enhanced by 3‐day lithium treatment. The results, therefore, indicate that subacute or chronic in vivo lithium treatment reduces agonist‐stimulated inositol phospholipid metabolism in cerebral cortex; this persistent inhibition appears to be at the level of G‐protein–phospholipase C coupling.