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 language | English |
|---|---|
| Pages (from-to) | 2402-2409 |
| Number of pages | 8 |
| Journal | Journal of Neurochemistry |
| Volume | 66 |
| Issue number | 6 |
| State | Published - Jun 1 1996 |
| Externally published | Yes |
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Keywords
- Bipolar affective disorder
- Depression
- Inositol
- Lithium
- Mania
- Phosphoinositide hydrolysis
ASJC Scopus subject areas
- Biochemistry
- Cellular and Molecular Neuroscience
Cite this
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 journal › Article
}
TY - JOUR
T1 - The phosphoinositide signal transduction system is impaired in bipolar affective disorder brain
AU - Jope, Richard S
AU - Song, Ling
AU - Li, Peter P.
AU - Young, L. Trevor
AU - Kish, Stephen J.
AU - Pacheco, Mary A.
AU - Warsh, Jerry J.
PY - 1996/6/1
Y1 - 1996/6/1
N2 - 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.
AB - 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.
KW - Bipolar affective disorder
KW - Depression
KW - Inositol
KW - Lithium
KW - Mania
KW - Phosphoinositide hydrolysis
UR - http://www.scopus.com/inward/record.url?scp=0029950633&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0029950633&partnerID=8YFLogxK
M3 - Article
C2 - 8632163
AN - SCOPUS:0029950633
VL - 66
SP - 2402
EP - 2409
JO - Journal of Neurochemistry
JF - Journal of Neurochemistry
SN - 0022-3042
IS - 6
ER -