The present address of Dr. L. T. Young is Department of Psychiatry, McMaster University, Hamilton, Ontario, Canada.
The Phosphoinositide Signal Transduction System Is Impaired in Bipolar Affective Disorder Brain
Article first published online: 23 NOV 2002
Journal of Neurochemistry
Volume 66, Issue 6, pages 2402–2409, June 1996
How to Cite
Jope, R. S., Song, L., Li, P. P., Young, L. T., Kish, S. J., Pacheco, M. A. and Warsh, J. J. (1996), The Phosphoinositide Signal Transduction System Is Impaired in Bipolar Affective Disorder Brain. Journal of Neurochemistry, 66: 2402–2409. doi: 10.1046/j.1471-4159.1996.66062402.x
- Issue published online: 23 NOV 2002
- Article first published online: 23 NOV 2002
- Received August 24, 1995; revised manuscript received December 19, 1995; accepted January 9, 1996.
- Bipolar affective disorder;
- Phosphoinositide hydrolysis;
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.