Effects of acute and chronic morphine treatment of calmodulin activity of rat brain.
The cyclic AMP-phosphodiesterase assay was used to quantitate the amount of calmodulin activity in various brain areas of male rats treated acutely or chronically for 5 days with morphine. The acute treatment with morphine decreased calmodulin activity in the mitochondrial-synaptosomal P2 fraction of the striatum, midbrain, and thalamus but had no effect on the cerebellum, which contains a low density of opiate receptors. The decrease in calmodulin activity by morphine was dose-dependent and was blocked by the opiate antagonist naloxone. In contrast, chronic treatment of rats with morphine increased calmodulin activity in the mitochondrial-synaptosomal P2 of the striatum, midbrain, cerebral cortex, and thalamus. A highly sensitive Ca2+/Mg2+-ATPase assay was also used to quantitate the amount of calmodulin activity in subcellular fractions obtained from the striatum. Chronic morphine treatment caused a significant increase in calmodulin activity in the membrane containing microsomal, synaptosomal, and mitochondrial layers but only a small change in the layer that contained the soluble proteins and the synaptic vesicles. It is suggested that alteration of the content of calmodulin in specific subcellular sites may have a central role in opiate action and addiction via regulation of multiple calmodulin-sensitive biochemical pathways.
D015105:3',5'-Cyclic-AMP Phosphodiesterases / Q000032:analysis; D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D017301:Ca(2+) Mg(2+)-ATPase; D002135:Calcium-Binding Proteins / Q000032:analysis*; D000252:Calcium-Transporting ATPases; D002147:Calmodulin / Q000032:analysis*; D003342:Corpus Striatum / Q000201:enzymology; D006801:Humans; D008297:Male; D009020:Morphine / Q000494:pharmacology*; D009021:Morphine Dependence / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains
D002135:Calcium-Binding Proteins; D002147:Calmodulin; D009020:Morphine; D015105:3',5'-Cyclic-AMP Phosphodiesterases; D017301:Ca(2+) Mg(2+)-ATPase; D000252:Calcium-Transporting ATPases