ALTERED PROTEIN-PHOSPHORYLATION IN THE RAT-BRAIN FOLLOWING CHRONIC LITHIUM AND CARBAMAZEPINE TREATMENTS

Lithium and carbamazepine (CBZ) alter levels of specific kinase-activa ting second messengers generated by adenylate cyclases and the phospho inositide 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 c hronic effects of lithium and CBZ on protein phosphorylation in the ra t brain by using quantitative autoradiography. Long-term treatments yi elded plasma levels within the therapeutic range. In the particulate h ippocampal fraction PKA-mediated phosphorylation of a 42 kDa protein a nd PKC-mediated phosphorylation of a 88 kDa protein were decreased aft er lithium treatment. In the cortical particulate fraction approximate ly 30% reduction in the PKA-mediated protein phosphorylation of severa l proteins was observed after lithium and CBZ treatments. In the same fraction, CBZ treatment significantly reduced PKC-mediated phosphoryla tion of several substrates by 30-40%. PKA activity was significantly r educed in cortex, but not in the hippocampus. Thus, both drugs exhibit ed fraction and region specificities. (C) 1997 Elsevier Science B.V.