The role of calmodulin in opioid-induced changes in the phosphorylation of rat striatal synaptic membrane proteins.

Chronic morphine treatment of rats decreased the level of phosphorylation of synaptic membrane proteins of the striatum assayed in vitro. Although the patterns of phosphorylated proteins separated on SDS-gel electrophoresis from morphine-tolerant rats resembled patterns produced by lowering Ca2+ levels in the assay, supplementation of the protein kinase assay with Ca2+ and its binding protein, calmodulin, did not restore full kinase activity. The addition of methadone or etorphine to the protein kinase in vitro however, was able to block the Ca2+-calmodulin stimulation of phosphorylation in both synaptic membranes and intact synaptosomes. These data suggest that opioids produce an irreversible (or slowly reversible) defect in the Ca2+-dependent protein kinase system of striatal membranes.