The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain

Richard S Jope, Ling Song, Peter P. Li, L. Trevor Young, Stephen J. Kish, Mary A. Pacheco, Jerry J. Warsh

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

The function of the phosphoinositide second messenger system was assessed in occipital, temporal, and frontal cortex obtained postmortem from subjects with bipolar affective disorder and matched controls by measuring the hydrolysis of [3H]phosphatidylinositol ([3H]PI) incubated with membrane preparations and several different stimulatory agents. Phospholipase C activity, measured in the presence of 0.1 mM Ca2+ to stimulate the enzyme, was not different in bipolar and control samples. G proteins coupled to phospholipase C were concentration-dependently activated by guanosine 5'-O- (3-thiotriphosphate) (GTPγS) and by NaF. GTPγS-stimulated [3H]PI hydrolysis was markedly lower (50%) at all tested concentrations (0.3-10 μM GTPγS) in occipital cortical membranes from bipolar compared with control subjects. Responses to GTPγS in temporal and frontal cortical membranes were similar in bipolars and controls, as were responses to NaF in all three regions. Brain lithium concentrations correlated directly with GTPγS- stimulated [3H]PI hydrolysis in bipolar occipital, but not temporal or frontal, cortex. Carbachol, histamine, trans-1-aminocyclopentyl-1,3- dicarboxylic acid, serotonin, and ATP each activated [3H]PI hydrolysis above that obtained with GTPγS alone, and these responses were similar in bipolars and controls except for deficits in the responses to carbachol and serotonin in the occipital cortex, which were equivalent to the deficit detected with GTPγS alone. Thus, among the three cortical regions examined there was a selective impairment in G protein-stimulated [3H]PI hydrolysis in occipital cortical membranes from bipolar compared with control subjects. These results directly demonstrate decreased activity of the phosphoinositide signal transduction system in specific brain regions in bipolar affective disorder.

Original languageEnglish
Pages (from-to)2402-2409
Number of pages8
JournalJournal of Neurochemistry
Volume66
Issue number6
StatePublished - Jun 1 1996
Externally publishedYes

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Signal transduction
Phosphatidylinositols
Mood Disorders
Bipolar Disorder
Signal Transduction
Brain
Hydrolysis
Occipital Lobe
Membranes
Carbachol
Frontal Lobe
Type C Phospholipases
GTP-Binding Proteins
Serotonin
Guanosine 5'-O-(3-Thiotriphosphate)
Second Messenger Systems
Temporal Lobe
Lithium
Histamine
Adenosine Triphosphate

Keywords

  • Bipolar affective disorder
  • Depression
  • Inositol
  • Lithium
  • Mania
  • Phosphoinositide hydrolysis

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

Jope, R. S., Song, L., Li, P. P., Young, L. T., Kish, S. J., Pacheco, M. A., & Warsh, J. J. (1996). The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. Journal of Neurochemistry, 66(6), 2402-2409.

The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. / Jope, Richard S; Song, Ling; Li, Peter P.; Young, L. Trevor; Kish, Stephen J.; Pacheco, Mary A.; Warsh, Jerry J.

In: Journal of Neurochemistry, Vol. 66, No. 6, 01.06.1996, p. 2402-2409.

Research output: Contribution to journalArticle

Jope, RS, Song, L, Li, PP, Young, LT, Kish, SJ, Pacheco, MA & Warsh, JJ 1996, 'The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain', Journal of Neurochemistry, vol. 66, no. 6, pp. 2402-2409.
Jope RS, Song L, Li PP, Young LT, Kish SJ, Pacheco MA et al. The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. Journal of Neurochemistry. 1996 Jun 1;66(6):2402-2409.
Jope, Richard S ; Song, Ling ; Li, Peter P. ; Young, L. Trevor ; Kish, Stephen J. ; Pacheco, Mary A. ; Warsh, Jerry J. / The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain. In: Journal of Neurochemistry. 1996 ; Vol. 66, No. 6. pp. 2402-2409.
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