Subacute and Chronic In Vivo Lithium Treatment Inhibits Agonist‐ and Sodium Fluoride‐Stimulated Inositol Phosphate Production in Rat Cortex
- 1 February 1989
- journal article
- research article
- Published by Wiley in Journal of Neurochemistry
- Vol. 52 (2), 498-506
- https://doi.org/10.1111/j.1471-4159.1989.tb09148.x
Abstract
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 [3H]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 EC50 value. This inhibition was not affected by the concentration of LiCl in the assay buffer. Stimulation of inositol phosphate formation by 10 mM 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-HT2 bindings were unaltered by lithium, as was cortical phospholipase C activity and isoproterenol-stimulated cyclic AMP formation. [3H]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.Keywords
This publication has 30 references indexed in Scilit:
- Time and space — novel aspects of hormone actionTrends in Pharmacological Sciences, 1988
- A review of the biochemical and neuropharmacological actions of lithiumPsychological Medicine, 1987
- Agonist-stimulated phosphatidylinositol 4,5-bisphosphate metabolism in the nervous systemNeurochemistry International, 1986
- The pharmacokinetic profile of lithium in rat and mouse; An important factor in psychopharmacological investigation of the drugNeuropharmacology, 1986
- Protein kinase C as a bidirectional regulator of cell functionTrends in Pharmacological Sciences, 1985
- Phorbol esters inhibit agonist-induced [3H] inositol-1-phosphate accumulation in rat hippocampal slicesBiochemical and Biophysical Research Communications, 1984
- Current concepts on the mechanisms of action of antidepressant drugsPharmacology & Therapeutics, 1981
- Lithium Increases Serotonin Release and Decreases Serotonin Receptors in the HippocampusScience, 1981
- Regional Alterations in Rat Brain Neurotransmitter Systems Following Chronic Lithium TreatmentJournal of Neurochemistry, 1980
- Local Origin of Fibroblasts deduced from Sarcomas induced in Chimaeras by Implants of Pliable DisksNature, 1971