Lithium modulation of second messenger signal amplification in man: Inhibition of phosphatidylinositol- specific phospholipase C and adenylate cyclase activity

Richard P. Ebstein; Bernard Lerer; Estelle R. Bennett; Baruch Shapira; Seth Kindler; Zecharia Shemesh; Nurit Gerstenhaber

doi:10.1016/0165-1781(88)90138-2

Lithium modulation of second messenger signal amplification in man: Inhibition of phosphatidylinositol- specific phospholipase C and adenylate cyclase activity

Richard P. Ebstein^*
, Bernard Lerer
, Estelle R. Bennett
, Baruch Shapira
, Seth Kindler
, Zecharia Shemesh
, Nurit Gerstenhaber

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

41 Scopus citations

Abstract

The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E₁-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E₁) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

Original language	English
Pages (from-to)	45-52
Number of pages	8
Journal	Psychiatry Research
Volume	24
Issue number	1
DOIs	https://doi.org/10.1016/0165-1781(88)90138-2
State	Published - Apr 1988
Externally published	Yes

Keywords

Adenylate cyclase
lithium
phosphatidylinositol
phospholipase C
second messengers

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10.1016/0165-1781(88)90138-2

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title = "Lithium modulation of second messenger signal amplification in man: Inhibition of phosphatidylinositol- specific phospholipase C and adenylate cyclase activity",

abstract = "The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.",

keywords = "Adenylate cyclase, lithium, phosphatidylinositol, phospholipase C, second messengers",

author = "Ebstein, \{Richard P.\} and Bernard Lerer and Bennett, \{Estelle R.\} and Baruch Shapira and Seth Kindler and Zecharia Shemesh and Nurit Gerstenhaber",

year = "1988",

month = apr,

doi = "10.1016/0165-1781(88)90138-2",

language = "אנגלית",

volume = "24",

pages = "45--52",

journal = "Psychiatry Research",

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T1 - Lithium modulation of second messenger signal amplification in man

T2 - Inhibition of phosphatidylinositol- specific phospholipase C and adenylate cyclase activity

AU - Ebstein, Richard P.

AU - Lerer, Bernard

AU - Bennett, Estelle R.

AU - Shapira, Baruch

AU - Kindler, Seth

AU - Shemesh, Zecharia

AU - Gerstenhaber, Nurit

PY - 1988/4

Y1 - 1988/4

N2 - The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

AB - The activity of phosphatidylinositol-specific phospholipase C was significantly reduced in platelets obtained from 20 euthymic manic-depressive patients on therapeutic lithium doses (mean blood level 0.85 mEq/l) compared to an age- and sex-matched group of 36 control subjects. The activities of prostaglandin E1-, aluminum/NaF-, and forskolin-stimulated platelet adenylate cyclase activity were also measured in a similar group of 16 lithium-treated and 22 control subjects. A marked reduction in both postreceptor (aluminum/NaF and forskolin) and receptor-stimulated (prostaglandin E1) platelet adenylate cyclase activity was observed in the lithium-treated group (mean blood level 0.81 mEq/l). These findings support the hypothesis that lithium's therapeutic mode of action in manic-depressive psychosis is mediated by the combined down-regulation of both principal second messenger systems, inositol phosphates and cyclic adenosine monophosphate, by reducing the activity of phosphatidylinositol-specific phospholipase C and adenylate cyclase.

KW - Adenylate cyclase

KW - lithium

KW - phosphatidylinositol

KW - phospholipase C

KW - second messengers

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AN - SCOPUS:0023948931

SN - 0165-1781

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EP - 52

JO - Psychiatry Research

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IS - 1

ER -

Lithium modulation of second messenger signal amplification in man: Inhibition of phosphatidylinositol- specific phospholipase C and adenylate cyclase activity

Abstract

Keywords

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