ETHANOL AND PROTEIN-KINASE-C IN RAT-BRAIN

The effect of chronic ethanol consumption on the catalytic activity of protein kinase C isolated from rat brain was studied in two different ways. Enzyme activity was first measured by phosphorylation of Histon e IIIS in vitro. There was no change in the activity of the cytosolic enzyme. Membrane-associated enzyme activity was reduced in the ethanol -treated animal. This difference was not evident if the enzyme was sti mulated by arachidonate. The reduction in enzyme activity was confirme d by analysis of the phosphorylation of endogenous substrates in intac t synaptosomes. When the binding of the ligand [H-3]phorbol dibutyrate was measured by quantitative autoradiography, increased binding to me mbrane-associated protein kinase C was observed in the CA1 region of t he hippocampus but not in other brain regions. These results indicate that ethanol treatment results in a general reduction in membrane-asso ciated protein kinase C activity as measured in vitro but the effect m ay not be consistent in all brain regions. The differential effect in the CA1 region of the hippocampus may be a reflection of a disruption in the normal regulation of protein kinase C activity in this area and may indicate that this region is a sensitive target for the action of ethanol.