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Lithium Enhances Accumulation of [ 3 H]Inositol Radioactivity and Mass of Second Messenger Inositol 1,4,5‐Trisphosphate in Monkey Cerebral Cortex Slices
Author(s) -
Dixon John F.,
Lee Chang Ho,
Los Georgyi V.,
Hokin Lowell E.
Publication year - 1992
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.1471-4159.1992.tb10129.x
Subject(s) - inositol , inositol phosphate , inositol trisphosphate , second messenger system , endocrinology , medicine , in vivo , guinea pig , lithium (medication) , cerebral cortex , cortex (anatomy) , biology , inositol trisphosphate receptor , chemistry , receptor , biochemistry , neuroscience , microbiology and biotechnology
Abstract: We previously reported that lithium, in the presence of acetylcholine, increased accumulations of inositol 1,4,5‐trisphosphate and inositol 1,3,4,5‐tetrakisphosphate in brain cortex slices from the guinea pig, rabbit, rat, and mouse. In the mouse and rat, the Li + ‐induced increases required supplementation of the medium with inositol. This probably relates to the following facts: (a) Brain cortices of the mouse and rat contain in vivo concentrations of inositol half of that of the guinea pig. (b) Incubated rat brain cortex slices are depleted of inositol by 80%. (c) The slices require 10 m M inositol supplementation to restore in vivo concentrations. We now show that in monkey brain cortex slices, therapeutic concentrations of Li + increase accumulation of inositol 1,4,5‐trisphosphate. The inositol 1,3,4,5‐tetrakisphosphate level is not increased. Neither inositol nor an agonist is required. The same effects are seen whether inositol 1,4,5‐trisphosphate is quantified by the [ 3 H]inositol prelabeling technique or by mass assay, although mass includes a pool of inositol 1,4,5‐trisphosphate that is metabolically inactive. Thus, in a therapeutically relevant model for humans, Li + increases inositol 1,4,5‐trisphosphate levels in brain cortex slices, as was previously seen in lower mammals at non‐rate‐limiting concentrations of inositol.