The effects of etorphine on the carboxylmethylation of synaptosomal proteins of rat striatum

Abstract

The stimulation of protein carboxylmethyl transferase (PCMT) activity in rat striatal synaptosomes by the dopamine agonist, apomorphine, and a PCMT subtrate, calmodulin, was measured in normal and opioid-treated rats to see if inactivation of calmodulin by methylation is a factor in opioid action. Total carboxyl methyl acceptors were measured in preparations from alkaline homogenates, while those already occupied in vivo were measured in acidic homogenates, since the carboylmethyl group is stable in acid. The administration of etorphine acutely increased the number of already occupied acceptors while chronic morphine treatment decreased this number. Apomorphine stimulation of PCMT activity was significant only when tested for direction of change from control values. Calmodulin was a substrate for PCMT in all preparations. We conclude that the method of estimating total and occupied acceptors was partially successful. Perhaps a more alkaline homogenate would produce a synaptosomal prepration with a maximal PCMT activity. The importance of calmodulin carboxylmethylation cannot be assessed from these experiments, although the results shown in figure 3 suggest that opioid treatments have different effects on the methylation of calmodulin.