J Korean Soc Biol Psychiatry.  1998 Nov;5(2):227-234.

The Effects of Chronic Carbamazepine Administration on Protein Kinase A and Protein Kinase C Activities in Rat Brain

• Rheem DW
• Kim L
• Suh KY

Abstract

OBJECTIVE
Many evidences suggest that patients with bipolar disorder have functional abnormalities in their postreceptor signal transduction pathways, and mood stabilizing effect of lithium is exerted by modulating this dysfunctioning system. Carbamazepine, an antiepileptic agent, is also known to be effective in the treatment and prevention of bipolar disorder. But the precise mechanism of action of the drug is still poorly understood. This study was performed to elucidate the possible therapeutic mechanism of carbamazepine. METHOD: The effects of chronic carbamazepine administration on protein kinase A and protein kinase C activities in frontal cortex of rat brain after 2 weeks of drug administration were measured and compared with those of control subjects.
RESULTS
Mean(+/-SE) value of activity(phosphate transfer micromol/mg of protein, min) or protein kinase A in control and test group was 0.249563+/-0.036 and 0.539853+/-0.078, and that of protein kinase C was 0.654817+/-0.053 and 1.146205+/-0.052 respectively, being increased in test group. And differences between the two groups were statistically significant for both enzymes(protein kinase A ; p<0.01, protein kinase C ;p<0.001).
CONCLUSION
These results show that chronic carbamazepine administration increases protein kinase A and C activities, and concerning the possible mode of therapeutic action in bipolar disorder it is suggested that enhanced enzymes phosphorylate receptor-G-protein-effector complexes to dampen hyperfunctioning neuronal activity and thus stabilize the system.

MeSH Terms

Animals
Bipolar Disorder
Brain*
Carbamazepine*
Cyclic AMP-Dependent Protein Kinases*
Humans
Lithium
Neurons
Phosphotransferases
Protein Kinase C*
Protein Kinases*
Rats*
Second Messenger Systems
Signal Transduction
Carbamazepine
Cyclic AMP-Dependent Protein Kinases
Lithium
Phosphotransferases
Protein Kinase C
Protein Kinases