Altered protein phosphorylation in the rat brain following chronic lithium and carbamazepine treatments.

Lithium and carbamazepine (CBZ) alter levels of specific kinase-activating second messengers generated by adenylate cyclases and the phosphoinositide system. Thus, lithium and CBZ may change endogenous protein phosphorylation mediated by cyclic AMP-dependent protein kinase (PKA) and protein kinase C (PKC). The present study aimed at comparing the chronic effects of lithium and CBZ on protein phosphorylation in the rat brain by using quantitative autoradiography. Long-term treatments yielded plasma levels within the therapeutic range. In the particulate hippocampal fraction PKA-mediated phosphorylation of a 42 kDa protein and PKC-mediated phosphorylation of a 88 kDa protein were decreased after lithium treatment. In the cortical particulate fraction approximately 30% reduction in the PKA-mediated protein phosphorylation of several proteins was observed after lithium and CBZ treatments. In the same fraction, CBZ treatment significantly reduced PKC-mediated phosphorylation of several substrates by 30-40%. PKA activity was significantly reduced in cortex, but not in the hippocampus. Thus, both drugs exhibited fraction and region specificities.