The effect of opioids on striatal calmodulin levels.

Phosphorylation of proteins in synaptic membranes of rat striatum by endogenous kinases was quantified by scanning the optical density on radioautograms made from gels after electrophoresis of assay samples. Neither the decreased phosphorylation found in samples from morphine-tolerant rats could be raised to control levels, nor could samples from untreated rats be raised to those found after acute opioid administration by the addition of Ca++ and calmodulin to the assay. However, the addition of opioids in vitro to the assay was able to inhibit the stimulation of protein kinase activity by Ca++ and calmodulin. Calmodulin seemed to be transported from membranes to cytosol of striatal synaptosomes from morphine tolerant rats. This phenomenon has been related to striatal dopamine receptor supersensitivity (5, 10), a condition suggested by many kinds of evidence in tolerant animals. After acute administration of etorphine or methionine-enkephalin, the levels of calmodulin were increased in both compartments of striatal synaptosomes. The increased membranal levels may be related to its ease of extraction from the membranes and thus to a physical change in calmodulin.