Acute and chronic lithium treatments influence agonist and depolarization-stimulated inositol phospholipid hydrolysis in rat cerebral cortex.
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 microM carbachol (muscarinic), 31 mM K+, 300 microM histamine (H1) and 300 microM 5-hydroxytryptamine (5-hydroxytryptamine2) were reduced significantly even after preincubation of slices with 2.5 mM myo-inositol. However, the response to noradrenaline (100 microM) (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 When rats were withdrawn from chronic treatment for 18 hr, the responses to carbachol were enhanced significantly with respect to untreated controls.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 less than [1 mM] in cerebral tissue, severely disrupts phosphoinositide metabolism. Although such effects may well be secondary to inhibition of inositol-monophosphatase, they are not reversed by inositol and therefore do not appear to result from depleted phosphoinositides.
D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D006632:Histamine / Q000494:pharmacology; D006868:Hydrolysis; D007294:Inositol / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009638:Norepinephrine / Q000494:pharmacology; D010716:Phosphatidylinositols / Q000378:metabolism*; D011188:Potassium / Q000494:pharmacology; D051381:Rats; D011919:Rats, Inbred Strains; D012701:Serotonin / Q000494:pharmacology
D010716:Phosphatidylinositols; D012701:Serotonin; D007294:Inositol; D006632:Histamine; D002217:Carbachol; D008094:Lithium; D011188:Potassium; D009638:Norepinephrine