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Inositol 1,4,5-trisphosphate accumulation in brain of lithium-treated rats

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Lipids

Abstract

The mechanism of action of lithium as a drug for patients with affective disorders was investigated. Three-week-old male rats were orally administered 2.7 mEq Li2CO3/kg/d for 1 or 3 wk, and phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), inositol phosphate (IP), inositol diphosphate (IP2) and inositol triphosphate (IP3) levels in brain were measured. The levels of IP were increased 1.7 and 2.4 times after 1 wk and 3 wk of lithium administration, respectively, while PI, PIP, PIP2, IP2 and IP3 levels were not altered. IP3 was further fractionated by high-performance liquid chromatography into I-1,3,4-P3 and I-1,4,5-P3. In the control rat brain, the relative percentages of I-1,3,4-P3 and I-1,4,5-P3 were 95.8 and 4.2, respectively. However, after 3 wk of lithium administration, the values were changed to 69.6 and 30.3%, respectively. This increase in the neurotransducer I-1,4,5-P3 in the brain may be relevant to the mechanism of action in the lithium treatment of patients with manic-depressive disorders.

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Abbreviations

DPO:

2-5-diphenyloxazole

HPLC:

high-performance liquid chromatography

HPTLC:

high-performance thin-layer chromatography

I-1,3,4-P:

inositol 1,3,4-trisphosphate

I-1,4,5-P3 :

inositol 1,4,5-trisphosphate

IP:

inositol phosphate

I-1-P:

inositol 1-phosphate

IP2 :

inositol diphosphate(s)

IP3 :

inositol triphosphate(s)

IP4 :

inositol tetraphosphate(s)

PC:

phosphatidylcholine

PE:

phosphatidylethanolamine

PI:

phosphatidylinositol

PIP:

phosphatidylinositol 4-phosphate

PIP2 :

phosphatidylinositol 4,5-bisphosphate

POPOP:

1,4-bis[2-(5-phenyloxazolyl)]benzene

TLC:

thin-layer chromatography

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Author notes

  1. Yoshio Ishima

    Present address: Ishima Institute for Neurosciences, 11-7 Higashi-Sanchome, 186, Kunitachi-Shi, Tokyo, Japan

Authors and Affiliations

  1. Department of Neuropsychiatry, Ibaraki Prefectural Hospital, 309-17, Tomobe, Ibaraki, Japan

    Yoshio Ishima

  2. Faculty of Pharmaceutical Sciences, Teikyo University, Sagamiko, 199-01, Kanagawa, Japan

    Michiyo Fujimagari, Yasuo Masuzawa & Keizo Waku

Authors
  1. Yoshio Ishima
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  2. Michiyo Fujimagari
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  3. Yasuo Masuzawa
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  4. Keizo Waku
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Ishima, Y., Fujimagari, M., Masuzawa, Y. et al. Inositol 1,4,5-trisphosphate accumulation in brain of lithium-treated rats. Lipids 28, 577–581 (1993). https://doi.org/10.1007/BF02536049

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  • DOI: https://doi.org/10.1007/BF02536049

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