ACUTE AND CHRONIC LITHIUM TREATMENTS INFLUENCE AGONIST AND DEPOLARIZATION-STIMULATED INOSITOL PHOSPHOLIPID HYDROLYSIS IN RAT CEREBRAL-CORTEX
- 1 June 1987
- journal article
- research article
- Vol. 241 (3), 1023-1027
Abstract
The ability of acute and chronic Li treatment to influence agonist and depolarization-induced phosphoinositide metabolism was examined in rat cerebral cortex slices. After acute treatment (6.75 mEq/kg, 18 hr), [3H]inositol phosphates accumulating in the presence of 100 .mu.M carbachol (muscarinic), 31 mM K+, 300 .mu.M histamine (H1) and 300 .mu.M 5-hydroxytryptamine (5-hydroxytryptamine2) were reduced significantly even after preincubation of slices with 2.5 mM myo-inositol. However, the response to noradrenaline (100 .mu.M) (alpha-1) was unaffected. In the absence of a drug-free period, chronic Li (2 weeks) maintained the reduced phosphoinositide response to receptor agonists and K+, and now even noradrenaline responses were reduced significantly. Dose-response curves revealed that reduction in the response to carbachol was due to a fall in maximal response and not in EC50. When rats were withdrawn from chronic treatment for 18 hr, the responses to carbachol were enhanced significantly with respect to untreated controls. Neither acute nor chronic Li treatments altered significantly the overall incorporation of [3H]inositol into phospholipids. Furthermore, Li treatment did not influence the activity of phospholipase C assayed in crude homogenates of cerebral cortex. In conclusion, acute and chronic Li treatments producing < [1 mM] in cerebral tissue, severely disrupts phosphoinositide metabolism. Although such effects may well be secondary to inhibition of inositolmonophosphatase, they are not reversed by inositol and therefore do not appear to result from depleted phosphoinositides.This publication has 17 references indexed in Scilit:
- Phorbol esters inhibit agonist-induced [3H] inositol-1-phosphate accumulation in rat hippocampal slicesBiochemical and Biophysical Research Communications, 1984
- Relationship between inositol polyphosphate production and the increase of cytosolic free Ca2+ induced by vasopressin in isolated hepatocytes.Journal of Biological Chemistry, 1984
- Inositol Phospholipid Hydrolysis in Rat Cerebral Cortical Slices: I. Receptor CharacterisationJournal of Neurochemistry, 1984
- THYROTROPIN-RELEASING HORMONE-STIMULATED [INOSITOL-H-3 METABOLISM IN GH3 PITUITARY-TUMOR CELLS - STUDIES WITH LITHIUM1984
- Lithium amplifies agonist-dependent phosphatidylinositol responses in brain and salivary glandsBiochemical Journal, 1982
- Evidence that Lithium Alters Phosphoinositide Metabolism: Chronic Administration Elevates Primarily d‐myo‐Inositol‐1‐Phosphate in Cerebral Cortex of the RatJournal of Neurochemistry, 1981
- The effects of lithium ion and other agents on the activity of myo-inositol-1-phosphatase from bovine brain.Journal of Biological Chemistry, 1980
- Regional Alterations in Rat Brain Neurotransmitter Systems Following Chronic Lithium TreatmentJournal of Neurochemistry, 1980
- THE EFFECT OF LITHIUM ON NORADRENALINE-INDUCED CYCLIC-AMP ACCUMULATION IN RAT-BRAIN - INHIBITION AFTER CHRONIC TREATMENT AND ABSENCE OF SUPER-SENSITIVITY1980
- Increased brain myo-inositol 1-phosphate in lithium-treated ratsBiochemical and Biophysical Research Communications, 1976