title: Lithium reduces the accumulation of inositol polyphosphate second messengers following cholinergic stimulation of cerebral cortex slices.
abstract: The ability of lithium to interfere with the metabolism of inositol phosphates in brain may underlie its therapeutic action in manic-depressive illness. In these experiments, lithium, at therapeutic concentrations, enhanced the accumulation of [3H]inositol monophosphate but suppressed the accumulation of the putative second messengers [3H]inositol 1,4,5-trisphosphate [( 3H]Ins(1,4,5)P3) and [3H]inositol 1,3,4,5-tetrakisphosphate following stimulation of cerebral cortex slices with carbachol. Mass measurements of Ins(1,4,5)P3 showed similar inhibitory effects, which could be prevented by preincubation with myo-inositol. These data may reveal the mechanism by which lithium can reduce polyphosphoinositide-mediated neurotransmission in brain.
authors: Department of Pharmacology and Therapeutics, University of Leicester, England.
authors: E D
authors: ED
authors: Kennedy
authors: R A
authors: RA
authors: Challiss
authors: S R
authors: SR
authors: Nahorski
mesh_terms: D000818:Animals; D002217:Carbachol / Q000494:pharmacology; D002540:Cerebral Cortex / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D007295:Inositol Phosphates / Q000037:antagonists & inhibitors* / Q000378:metabolism; D008094:Lithium / Q000494:pharmacology*; D010277:Parasympathomimetics / Q000494:pharmacology*; D051381:Rats; D015290:Second Messenger Systems / Q000187:drug effects*; D013268:Stimulation, Chemical
chemical_list: D007295:Inositol Phosphates; D010277:Parasympathomimetics; D002217:Carbachol; D008094:Lithium