Increase of calmodulin-stimulated striatal particulate phosphorylation response in chronic haloperidol-treated rats.
Calcium- and calmodulin-dependent protein kinase and phosphatase activities were studied in rat striatal particulate preparations. The effect of Ca2+ (0.1-0.5 mM) on phosphorylation was completely abolished in the preparation which had been washed 3 times with a buffer containing ethylene glycol bis-(beta-aminoethyl ether)-N,N'-tetraacetic acid (EGTA, 1.2 mM). Ca2+-stimulated phosphorylation was restored in a dose-dependent manner after calmodulin (1 microgram) was added to the assays. Ca2+ and calmodulin promoted the phosphate incorporation into two major striatal protein bands with estimated Mr at 52 and 40 kdaltons. The presence of phosphatase in the EGTA-pretreated preparations was negligible. Chronic treatment in rats with haloperidol (1 mg/kg, 20 days) produced a significant decrease in the Ca2+-independent phosphorylation but an increase in the extent of Ca2+ and calmodulin-dependent phosphorylation in the striatum. The chronic haloperidol treatment did not alter the striatal [125I]calmodulin binding curve. In vitro, haloperidol (even at 10(-4) M) had no effect on calmodulin-dependent phosphorylation. Haloperidol (10(-4) M) did not reduce the number but decreased the rate of [125I]calmodulin bindign to the striatal particulates. These data suggest that the link between dopamine receptors and calmodulin-dependent enzyme is dissociated in vitro. On the other hand, the potentiated sensitivity of calmodulin-dependent protein kinase in the chronic haloperidol-treated rats correlated with the supersensitive dopamine receptor responses occurred in these rats. Therefore, calmodulin-dependent protein kinase may biochemically regulate dopamine receptor functions in the striatum in vivo.
D000818:Animals; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000502:physiology*; D003342:Corpus Striatum / Q000378:metabolism*; D004533:Egtazic Acid / Q000494:pharmacology; D006220:Haloperidol / Q000494:pharmacology*; D066298:In Vitro Techniques; D008297:Male; D009419:Nerve Tissue Proteins / Q000378:metabolism; D010750:Phosphoproteins / Q000378:metabolism; D010744:Phosphoric Monoester Hydrolases / Q000378:metabolism*; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains
D002147:Calmodulin; D009419:Nerve Tissue Proteins; D010750:Phosphoproteins; D004533:Egtazic Acid; D011494:Protein Kinases; D010744:Phosphoric Monoester Hydrolases; D006220:Haloperidol; D002118:Calcium