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.
Jensen
J B
JB
Department of Pharmacology, Panum Institute, University of Copenhagen, Denmark.
Mørk
A
A
D000818:Animals; D018692:Antimanic Agents / Q000494:pharmacology*; D001345:Autoradiography; D001921:Brain / Q000201:enzymology; D001923:Brain Chemistry / Q000187:drug effects*; D002220:Carbamazepine / Q000494:pharmacology*; D017868:Cyclic AMP-Dependent Protein Kinases / Q000378:metabolism; D004591:Electrophoresis, Polyacrylamide Gel; D066298:In Vitro Techniques; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar
D018692:Antimanic Agents; D009419:Nerve Tissue Proteins; D002220:Carbamazepine; D008094:Lithium; D017868:Cyclic AMP-Dependent Protein Kinases; D011493:Protein Kinase C