The high affinity inositol transport system -implications for the pathophysiology and treatment of bipolar disorder

Dietrich Van Calker; Robert H. Belmaker

doi:10.1034/j.1399-5618.2000.020203.x

The high affinity inositol transport system -implications for the pathophysiology and treatment of bipolar disorder

Dietrich Van Calker, Robert H. Belmaker

Research output: Contribution to journal › Short survey › peer-review

53 Scopus citations

Abstract

The 'inositol-depletion hypothesis' postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.

Original language	English
Pages (from-to)	102-107
Number of pages	6
Journal	Bipolar Disorders
Volume	2
Issue number	2
DOIs	https://doi.org/10.1034/j.1399-5618.2000.020203.x
State	Published - 1 Jan 2000

Keywords

Inositol depletion
Mood stabilizers
Myo-inositol uptake

ASJC Scopus subject areas

Psychiatry and Mental health
Biological Psychiatry

Access to Document

10.1034/j.1399-5618.2000.020203.x

Cite this

@article{ca737c1b8bcb4d1c9dfe41d555e8ab2d,

title = "The high affinity inositol transport system -implications for the pathophysiology and treatment of bipolar disorder",

abstract = "The 'inositol-depletion hypothesis' postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.",

keywords = "Inositol depletion, Mood stabilizers, Myo-inositol uptake",

author = "\{Van Calker\}, Dietrich and Belmaker, \{Robert H.\}",

year = "2000",

month = jan,

day = "1",

doi = "10.1034/j.1399-5618.2000.020203.x",

language = "English",

volume = "2",

pages = "102--107",

journal = "Bipolar Disorders",

issn = "1398-5647",

publisher = "Blackwell Munksgaard",

number = "2",

}

TY - JOUR

T1 - The high affinity inositol transport system -implications for the pathophysiology and treatment of bipolar disorder

AU - Van Calker, Dietrich

AU - Belmaker, Robert H.

PY - 2000/1/1

Y1 - 2000/1/1

N2 - The 'inositol-depletion hypothesis' postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.

AB - The 'inositol-depletion hypothesis' postulates that the therapeutic effects of lithium are due to inhibition of inositol monophosphatase, which leads to depletion of brain cells of myo-inositol and consequently to dampening of phosphoinositide (PI) signaling. This article examines the potential relevance of an alternative mechanism for inositol depletion: inhibition of myo-inositol uptake that proceeds via the sodium/myo-inositol cotransport (SMIT). We discuss recent in vitro experiments that show a pronounced downregulation of SMIT after chronic treatment with lithium, carbamazepine, and valproate at therapeutically relevant concentrations. It is concluded that downregulation of SMIT could represent a common mechanism of action of mood stabilizers.

KW - Inositol depletion

KW - Mood stabilizers

KW - Myo-inositol uptake

UR - https://www.scopus.com/pages/publications/0034209028

U2 - 10.1034/j.1399-5618.2000.020203.x

DO - 10.1034/j.1399-5618.2000.020203.x

M3 - Short survey

AN - SCOPUS:0034209028

SN - 1398-5647

VL - 2

SP - 102

EP - 107

JO - Bipolar Disorders

JF - Bipolar Disorders

IS - 2

ER -

The high affinity inositol transport system -implications for the pathophysiology and treatment of bipolar disorder

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this