Abbreviations used : BD, bipolar affective disorder ; C subunit, catalytic subunit ; G protein, guanine nucleotide binding protein ; PKA, cyclic AMP-dependent protein kinase ; R subunit, regulatory subunit.
Increased Cyclic AMP-Dependent Protein Kinase Activity in Postmortem Brain from Patients with Bipolar Affective Disorder
Article first published online: 13 JUN 2002
Journal of Neurochemistry
Volume 73, Issue 4, pages 1704–1710, October 1999
How to Cite
Fields, A., Li, P. P., Kish, S. J. and Warsh, J. J. (1999), Increased Cyclic AMP-Dependent Protein Kinase Activity in Postmortem Brain from Patients with Bipolar Affective Disorder. Journal of Neurochemistry, 73: 1704–1710. doi: 10.1046/j.1471-4159.1999.731704.x
- Issue published online: 13 JUN 2002
- Article first published online: 13 JUN 2002
- Bipolar disorder;
- Cyclic AMP;
- Cyclic AMP-dependent protein kinase;
- Postmortem brain.
Abstract : Previous observations of reduced [3H]cyclic AMP binding in postmortem brainregions frombipolar affective disorder subjects imply cyclic AMP-dependent proteinkinase functionmay be altered in this illness. To test this hypothesis, basal and stimulated cyclic AMP-dependent protein kinase activity was determined in cytosolic and particulate fractions of postmortem brain from bipolar disorder patients and matched controls. Maximal enzyme activity was significantly higher (104%) in temporal cortex cytosolic fractions from bipolar disorder brain compared with matched controls. In temporal cortex particulate fractions and in the cytosolic and particulate fractions of other brain regions, smaller but statistically nonsignificant increments in maximal enzyme activity were detected. Basal cyclic AMP-dependent protein kinase activity was also significantly higher (40%) in temporal cortex cytosolic fractions of bipolar disorder brain compared with controls. Estimated EC50 values for cyclic AMP activation of this kinase were significantly lower (70 and 58%, respectively) in both cytosolic and particulate fractions of temporal cortex from bipolar disorder subjects compared with controls. These findings suggest that higher cyclic AMP-dependent proteinkinase activity in bipolar disorder brain may be associated with a reduction of regulatory subunits of this enzyme, reflecting a possible adaptive response of this transducing enzyme to increased cyclic AMP signaling in this disorder.