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Measurement of Lithium‐Induced Changes in Mouse Inositol(1)Phosphate Levels In Vivo
Author(s) -
Atack John R.,
Cook Susan M.,
Watt Alan P.,
Ragan C. Ian
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.tb11031.x
Subject(s) - in vivo , lithium (medication) , inositol , inositol phosphate , phosphate , chemistry , biochemistry , medicine , endocrinology , biology , genetics , receptor
An anion‐exchange HPLC mass assay was used to characterize Swiss‐Webster mouse brain and peripheral tissue inositol(1)phosphate [Ins(1)P] levels. Ins(1)P was identified in all tissues studied but Ins(4)P could be identified only in brain, and then only as a part of a peak containing an additional, unidentified component. As a result, it was not possible to quantify Ins(4)P levels. Following a single subcutaneous dose of lithium (10 mmol/kg), brain Ins(1)P levels were maximally elevated after 6 h (corresponding to peak brain lithium concentrations) and were increased to levels 35‐ and 20‐fold higher than in saline‐treated animals in cholinergic agonist (pilocarpine)‐stimulated and unstimulated animals, respectively. The ED 50 for the lithium‐induced accumulation of brain Ins(1)P 6 h after administration was 4–6 mmol/kg. The pilocarpine stimulation of lithium‐induced brain Ins(1)P accumulation had an ED 50 of 22 mg/kg, with maximal accumulation occurring 120 min after pilocarpine administration. Atropine reduced Ins(1)P levels, in both the absence and the presence of lithium, by 40%, indicating that cholinergic systems contribute a large (40%) component of basal brain phosphatidylinositol (PI) cycle activity. In peripheral tissues, there were lithium‐induced accumulations of Ins(1)P in kidney, heart, and liver (but not testes) but these were less than that seen in the brain, suggesting that under basal (and pilocarpine‐stimulated) conditions, the brain has a higher turnover of the PI cycle than the various peripheral tissues studied. These data support the hypothesis that lithium exerts its effects in vivo via modulation of the PI cycle. In addition, the susceptibility of brain rather than peripheral tissue to the pharmacological effects of lithium may be a consequence of higher PI cycle turnover in brain.